Aging Dampens the Intestinal Innate Immune Response during Severe Clostridioides difficile Infection and Is Associated with Altered Cytokine Levels and Granulocyte Mobilization [Host Response and Inflammation]
This study explores the effect of age on cellular and cytokine immune responses during C. difficile infection. Young mice (2 to 3 months old) and aged mice (22 to 28 months old) were rendered susceptible to C. difficile infection with the antibiotic cefoperazone and then infected with C. difficile strains with varied disease-causing potentials. We observe that the host age and the infecting C. difficile strain influenced the severity of disease associated with infection. Tissue-specific CD45+ immune cell responses occurred at the time of peak disease severity in the ceca and colons of all mice infected with a high-virulenc...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Abernathy-Close, L., Dieterle, M. G., Vendrov, K. C., Bergin, I. L., Rao, K., Young, V. B. Tags: Host Response and Inflammation Source Type: research

The Lon-1 Protease Is Required by Borrelia burgdorferi To Infect the Mammalian Host [Molecular Pathogenesis]
Borrelia burgdorferi encodes a functional homolog of canonical Lon protease termed Lon-2. In addition, B. burgdorferi encodes a second Lon homolog called Lon-1. Recent studies suggest that Lon-1 may function differently from the prototypical Lon protease. However, the function of Lon-1 in B. burgdorferi biology remains virtually unknown. Particularly, the contribution of Lon-1 to B. burgdorferi fitness and infection remains hitherto unexplored. Herein, we show that Lon-1 plays a critical role for the infection of B. burgdorferi in a mammalian host. We found that lon-1 was highly expressed during animal infection, implying ...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Thompson, C., Mason, C., Parrilla, S., Ouyang, Z. Tags: Molecular Pathogenesis Source Type: research

Mycoplasma bovis Membrane Protein MilA Is a Multifunctional Lipase with Novel Lipid and Glycosaminoglycan Binding Activity [Molecular Pathogenesis]
The survival, replication, and virulence of mycoplasmas depend on their ability to capture and import host-derived nutrients using poorly characterized membrane proteins. Previous studies on the important bovine pathogen Mycoplasma bovis demonstrated that the amino-terminal end of an immunogenic 226-kDa (P226) protein, encoded by milA (the full-length product of which has a predicted molecular weight of 303 kDa), had lipase activity. The predicted sequence of MilA contains glycosaminoglycan binding motifs, as well as multiple copies of a domain of unknown function (DUF445) that is also found in apolipoproteins. We mutageni...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Adamu, J. Y., Wawegama, N. K., Kanci Condello, A., Marenda, M. S., Markham, P. F., Browning, G. F., Tivendale, K. A. Tags: Molecular Pathogenesis Source Type: research

EirA Is a Novel Protein Essential for Intracellular Replication of Coxiella burnetii [Molecular Pathogenesis]
The zoonotic bacterial pathogen Coxiella burnetii is the causative agent of Q fever, a febrile illness which can cause a serious chronic infection. C. burnetii is a unique intracellular bacterium which replicates within host lysosome-derived vacuoles. The ability of C. burnetii to replicate within this normally hostile compartment is dependent on the activity of the Dot/Icm type 4B secretion system. In a previous study, a transposon mutagenesis screen suggested that the disruption of the gene encoding the novel protein CBU2072 rendered C. burnetii incapable of intracellular replication. This protein, subsequently named Eir...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Kuba, M., Neha, N., Newton, P., Lee, Y. W., Bennett-Wood, V., Hachani, A., De Souza, D. P., Nijagal, B., Dayalan, S., Tull, D., McConville, M. J., Sansom, F. M., Newton, H. J. Tags: Molecular Pathogenesis Source Type: research

Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Apoptotic cell death can be an efficient defense reaction of mammalian cells infected with obligate intracellular pathogens; the host cell dies and the pathogen cannot replicate. While this is well established for viruses, there is little experimental support for such a concept in bacterial infections. All Chlamydiales are obligate intracellular bacteria, and different species infect vastly different hosts. Chlamydia trachomatis infects human epithelial cells; Parachlamydia acanthamoebae replicates in amoebae. We here report that apoptosis impedes growth of P. acanthamoebae in mammalian cells. In HeLa human epithelial cell...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Brokatzky, D., Kretz, O., Häcker, G. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Identification of Pathogenicity Island Genes Associated with Loss of Type IV Secretion Function during Murine Infection with Helicobacter pylori [Molecular Pathogenesis]
Chronic Helicobacter pylori colonization in animal models often leads to downregulation of the type IV secretion system (T4SS), typically by recombination in cagY, which is an essential T4SS gene. However, 17 other cag pathogenicity island (cagPAI) genes, as well as some non-cagPAI genes, are also essential for T4SS function. To get a more complete picture of how H. pylori regulates the T4SS during animal colonization, we examined cagY in 534 mouse-passaged isolates that lost T4SS function, defined as a normalized interleukin-8 (IL-8) value of
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Hansen, L. M., Dekalb, D. J., Cai, L. P., Solnick, J. V. Tags: Molecular Pathogenesis Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Tags: Spotlight Source Type: research

Combination of Mycobacterium indicus pranii and Heat-Induced Promastigotes Cures Drug-Resistant Leishmania Infection: Critical Role of Interleukin-6-Producing Classical Dendritic Cells [Microbial Immunity and Vaccines]
The major issues in available therapeutic modalities against leishmaniasis are cost, toxicity, and the emergence of drug resistance. The aim of this work was to develop a successful therapeutic adjuvant against drug-resistant Leishmania donovani infection by means of combining Mycobacterium indicus pranii with heat-induced promastigotes (HIP). One-month postinfected BALB/c mice were administered subcutaneously with M. indicus pranii (108 cells) and HIP (100 μg) for 5 days. Spleens were harvested for flow cytometric and reverse transcriptase PCR analysis. The antileishmanial effect of the combination strategy was associa...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Dey, S., Mukherjee, D., Sultana, S. S., Mallick, S., Dutta, A., Ghosh, J., Hussain, A., Sarkar, B., Mandal, S., Patra, P., Saha, B., Pal, C. Tags: Microbial Immunity and Vaccines Source Type: research

A Peptidoglycan Amidase Activator Impacts Salmonella enterica Serovar Typhimurium Gut Infection [Molecular Pathogenesis]
Salmonella enterica serovar Typhimurium is an important foodborne pathogen that causes diarrhea. S. Typhimurium elicits inflammatory responses and colonizes the gut lumen by outcompeting the microbiota. Although evidence is accumulating with regard to the underlying mechanism, the infectious stage has not been adequately defined. Peptidoglycan amidases are widely distributed among bacteria and play a prominent role in peptidoglycan maintenance by hydrolyzing peptidoglycans. Amidase activation is required for the regulation of at least one of two cognate activators, NlpD or EnvC (also called YibP). Recent studies establishe...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Nakamura, N., Hoshino, Y., Shiga, T., Haneda, T., Okada, N., Miki, T. Tags: Molecular Pathogenesis Source Type: research

Mice Lacking {gamma}{delta} T Cells Exhibit Impaired Clearance of Pseudomonas aeruginosa Lung Infection and Excessive Production of Inflammatory Cytokines [Host Response and Inflammation]
In this study, the role of T cells was examined in an acute mouse model of P. aeruginosa lung infection. In the absence of T cells, mice displayed impaired bacterial clearance and decreased survival, outcomes which were associated with delayed neutrophil recruitment and impaired recruitment of other immune cells (macrophages, T cells, natural killer cells, and natural killer T [NKT] cells) into the airways. Despite reduced NKT cell recruitment in the airways of mice lacking T cells, NKT cell-deficient mice exhibited wild-type level control of P. aeruginosa infection. Proinflammatory cytokines were also altered in T cell-de...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Omar, T., Ziltener, P., Chamberlain, E., Cheng, Z., Johnston, B. Tags: Host Response and Inflammation Source Type: research

Vibrio cholerae OmpR Contributes to Virulence Repression and Fitness at Alkaline pH [Molecular Pathogenesis]
Vibrio cholerae is a Gram-negative human pathogen and the causative agent of the life-threatening disease cholera. V. cholerae is a natural inhabitant of marine environments and enters humans through the consumption of contaminated food or water. The ability to transition between aquatic ecosystems and the human host is paramount to the pathogenic success of V. cholerae. The transition between these two disparate environments requires the expression of adaptive responses, and such responses are most often regulated by two-component regulatory systems such as the EnvZ/OmpR system, which responds to osmolarity and acidic pH ...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Kunkle, D. E., Bina, X. R., Bina, J. E. Tags: Molecular Pathogenesis Source Type: research

Chlamydia Deficient in Plasmid-Encoded pGP3 Is Prevented from Spreading to Large Intestine [Host-Associated Microbial Communities]
The cryptic plasmid pCM is critical for chlamydial colonization in the gastrointestinal tract. Nevertheless, orally inoculated plasmid-free Chlamydia sp. was still able to colonize the gut. Surprisingly, orally inoculated Chlamydia sp. deficient in only plasmid-encoded pGP3 was no longer able to colonize the gut. A comparison of live organism recoveries from individual gastrointestinal tissues revealed that pGP3-deficient Chlamydia sp. survived significantly better than plasmid-free Chlamydia sp. in small intestinal tissues. However, the small intestinal pGP3-deficient Chlamydia sp. failed to reach the large intestine, exp...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Huo, Z., He, C., Xu, Y., Jia, T., Wang, J., Zhong, G. Tags: Host-Associated Microbial Communities Source Type: research

Role of Pseudomonas aeruginosa Glutathione Biosynthesis in Lung and Soft Tissue Infection [Bacterial Infections]
In this study, we created a P. aeruginosa mutant defective in GSH biosynthesis to examine how loss of GSH biosynthesis affects P. aeruginosa virulence. We found that GSH is critical for normal growth in vitro and provides protection against hydrogen peroxide, bleach, and ciprofloxacin. We also studied the role of P. aeruginosa GSH biosynthesis in four mouse infection models, including the surgical wound, abscess, burn wound, and acute pneumonia models. We discovered that the GSH biosynthesis mutant was slightly less virulent in the acute pneumonia infection model but was equally virulent in the three other models. This wor...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Michie, K. L., Dees, J. L., Fleming, D., Moustafa, D. A., Goldberg, J. B., Rumbaugh, K. P., Whiteley, M. Tags: Bacterial Infections Source Type: research

Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity [Bacterial Infections]
To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been investigated. Here, we report that overexpression of an operon encoding a highly conserved inorganic phosphate importer, PstSCAB, increases the sensitivity of Staphylococcus aureus to calprotectin-med...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Kelliher, J. L., Brazel, E. B., Radin, J. N., Joya, E. S., Parraga Solorzano, P. K., Neville, S. L., McDevitt, C. A., Kehl-Fie, T. E. Tags: Bacterial Infections Source Type: research

Dual Function of Aar, a Member of the New AraC Negative Regulator Family, in Escherichia coli Gene Expression [Molecular Pathogenesis]
Enteroaggregative Escherichia coli (EAEC) is an E. coli pathotype associated with diarrhea and growth faltering. EAEC virulence gene expression is controlled by the autoactivated AraC family transcriptional regulator, AggR. AggR activates transcription of a large number of virulence genes, including Aar, which in turn acts as a negative regulator of AggR itself. Aar has also been shown to affect expression of E. coli housekeeping genes, including H-NS, a global regulator that acts at multiple promoters and silences AT-rich genes (such as those in the AggR regulon). Although Aar has been shown to bind both AggR and H-NS in ...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Mickey, A. S., Nataro, J. P. Tags: Molecular Pathogenesis Source Type: research

The ESX-1 Virulence Factors Downregulate miR-147-3p in Mycobacterium marinum-Infected Macrophages [Molecular Pathogenesis]
As important virulence factors of Mycobacterium tuberculosis, EsxA and EsxB not only play a role in phagosome rupture and M. tuberculosis cytosolic translocation but also function as modulators of host immune responses by modulating numerous microRNAs (miRNAs). Recently, we have found that mycobacterial infection downregulated miR-148a-3p (now termed miR-148) in macrophages in an ESX-1-dependent manner. The upregulation of miR-148 reduced mycobacterial intracellular survival. Here, we investigated miR-147-3p (now termed miR-147), a negative regulator of inflammatory cytokines (e.g., interleukin-6 [IL-6] and IL-10), in myco...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Zuo, X., Wang, L., Bao, Y., Sun, J. Tags: Molecular Pathogenesis Source Type: research

Enterococcus faecalis Manganese Exporter MntE Alleviates Manganese Toxicity and Is Required for Mouse Gastrointestinal Colonization [Molecular Pathogenesis]
In this study, we examine the role of the highly conserved MntE transporter in E. faecalis Mn homeostasis and virulence. We show that inactivation of mntE results in growth restriction in the presence of excess Mn, but not other metals, demonstrating its specific role in Mn detoxification. Upon growth in the presence of excess Mn, an mntE mutant accumulates intracellular Mn, iron (Fe), and magnesium (Mg), supporting a role for MntE in Mn and Fe export and a role for Mg in offsetting Mn toxicity. Growth of the mntE mutant in excess Fe also results in increased levels of intracellular Fe, but not Mn or Mg, providing further ...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Lam, L. N., Wong, J. J., Chong, K. K. L., Kline, K. A. Tags: Molecular Pathogenesis Source Type: research

Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection [Fungal and Parasitic Infections]
Chagas disease is a major public health issue, affecting ~10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of T. cruzi infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could m...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Horta, A. L., Williams, T., Han, B., Ma, Y., Menezes, A. P. J., Tu, V., Talvani, A., Weiss, L. M., Huang, H. Tags: Fungal and Parasitic Infections Source Type: research

Ursodeoxycholic Acid (UDCA) Mitigates the Host Inflammatory Response during Clostridioides difficile Infection by Altering Gut Bile Acids [Bacterial Infections]
Clostridioides difficile infection (CDI) is associated with increasing morbidity and mortality posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this enteric pathogen. Administration of the secondary bile acid ursodeoxycholic acid (UDCA; ursodiol) inhibits the life cycles of various strains of C. difficile in vitro, suggesting that the FDA-approved formulation of UDCA, known as ursodiol, may be able to restore colonization resistance against C. difficile in vivo. However, the mechanism(s) by which ursod...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Winston, J. A., Rivera, A. J., Cai, J., Thanissery, R., Montgomery, S. A., Patterson, A. D., Theriot, C. M. Tags: Bacterial Infections Source Type: research

Functional Properties of Helicobacter pylori VacA Toxin m1 and m2 Variants [Molecular Pathogenesis]
In this study, we generated H. pylori strains producing chimeric proteins in which VacA m1 segments of a parental strain were replaced by corresponding m2 sequences. In comparison to the parental m1 VacA protein, a chimeric protein (designated m2/m1) containing m2 sequences in the N-terminal portion of the m region was less potent in causing vacuolation of HeLa cells, AGS gastric cells, and AZ-521 duodenal cells and had reduced capacity to cause membrane depolarization or death of AZ-521 cells. Consistent with the observed differences in activity, the chimeric m2/m1 VacA protein bound to cells at reduced levels compared to...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Caston, R. R., Sierra, J. C., Foegeding, N. J., Truelock, M. D., Campbell, A. M., Frick-Cheng, A. E., Bimczok, D., Wilson, K. T., McClain, M. S., Cover, T. L. Tags: Molecular Pathogenesis Source Type: research

Role of {beta}2 Integrins in Neutrophils and Sepsis [Minireviews]
Sepsis remains medically challenging, with high morbidity and mortality. A novel intervention is urgently needed in the absence of specific, targeted therapy. Neutrophils act as double-edged swords in sepsis; they can help to eradicate microbes, but they also contribute to tissue injury. β2 integrins are critical adhesion molecules that regulate a number of neutrophil functions. β2 integrins consist of four members, namely, αLβ2, αMβ2, αXβ2, and αDβ2. Here, we review the role of each β2 integrin in neutrophils and sepsis and consider future direction for therapeuti...
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Authors: Yuki, K., Hou, L. Tags: Minireviews Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 20, 2020 Category: Infectious Diseases Tags: Masthead Source Type: research

The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease [Microbial Immunity and Vaccines]
In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding. We found that the sera from CspZ-YA-vaccinated mice more efficiently eliminated spirochetes and blocked CspZ FH-binding activity than sera from CspZ-immunized mice. We also found that vaccination with CspZ, but not CspZ-YA, triggered the production of anti-FH antibodies, justifying CspZ-YA as an LD vaccine candidate. The mechanistic and efficacy information derived from this study provides insights into the development of...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Marcinkiewicz, A. L., Lieknina, I., Yang, X., Lederman, P. L., Hart, T. M., Yates, J., Chen, W.-H., Bottazzi, M. E., Mantis, N. J., Kraiczy, P., Pal, U., Tars, K., Lin, Y.-P. Tags: Microbial Immunity and Vaccines Source Type: research

LuxS/AI-2 Quorum Sensing System in Edwardsiella piscicida Promotes Biofilm Formation and Pathogenicity [Bacterial Infections]
LuxS/AI-2 is an important quorum sensing system which affects the growth, biofilm formation, virulence, and metabolism of bacteria. LuxS is encoded by the luxS gene, but how this gene is associated with a diverse array of physiological activities in Edwardsiella piscicida (E. piscicida) is not known. Here, we constructed an luxS gene mutant strain, the luxS strain, to identify how LuxS/AI-2 affects pathogenicity. The results showed that LuxS was not found in the luxS gene mutant strain, and this gene deletion decreased E. piscicida growth compared to that of the wild-type strain. Meanwhile, the wild-type strain significant...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Sun, Y., Li, Y., Luo, Q., Huang, J., Chen, J., Zhang, R., Wang, X. Tags: Bacterial Infections Source Type: research

Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection [Host Response and Inflammation]
Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry and near-infrared spectroscopy, and the endothelial glycocalyx was assessed by sublingual videomicroscopy and measurement of biom...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Woodford, J., Yeo, T. W., Piera, K. A., Butler, K., Weinberg, J. B., McCarthy, J. S., Anstey, N. M., Barber, B. E. Tags: Host Response and Inflammation Source Type: research

Immune Profile of the Nasal Mucosa in Patients with Cutaneous Leishmaniasis [Fungal and Parasitic Infections]
Localized skin lesions are characteristic of cutaneous leishmaniasis (CL); however, Leishmania (Viannia) species, which are responsible for most CL cases in the Americas, can spread systemically, sometimes resulting in mucosal disease. Detection of Leishmania has been documented in healthy mucosal tissues (conjunctiva, tonsils, and nasal mucosa) and healthy skin of CL patients and in individuals with asymptomatic infection in areas of endemicity of L. (V.) panamensis and L. (V.) braziliensis transmission. However, the conditions and mechanisms that favor parasite persistence in healthy mucosal tissues are unknown. In this ...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Gomez-Zafra, M. J., Navas, A., Jojoa, J., Murillo, J., Gonzalez, C., Gomez, M. A. Tags: Fungal and Parasitic Infections Source Type: research

Generation and Evaluation of a Glaesserella (Haemophilus) parasuis Capsular Mutant [Bacterial Infections]
Glaesserella (Haemophilus) parasuis is a commensal bacterium of the upper respiratory tract in pigs and also the causative agent of Gla╠łsser’s disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation with isolate pathogenicity. To investigate the role the capsule plays in G. parasuis virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated (HS069cap) through allelic exchange following natural transformation. HS069cap was unable to cause signs of systemic ...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Eberle, K. C., Hau, S. J., Luan, S.-L., Weinert, L. A., Stasko, J. A., Wang, J., Peters, S. E., Langford, P. R., Rycroft, A. N., Wren, B. W., Maskell, D. J., Tucker, A. W., Brockmeier, S. L., on behalf of the BRaDP1T Consortium Tags: Bacterial Infections Source Type: research

Towards Innovative Design and Application of Recombinant Eimeria as a Vaccine Vector [Minireviews]
Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus Eimeria is widespread in domestic animals, causing serious coccidiosis. Eimeria parasites with strong immunogenicity are potent coccidiosis vaccine candidates and offer a valuable model of l...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Tang, X., Liu, X., Suo, X. Tags: Minireviews Source Type: research

Staphylococcus aureus Fibronectin Binding Protein A Mediates Biofilm Development and Infection [Bacterial Infections]
Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation. Staphylococcus aureus is a leading cause of biofilm-associated infections which persist due to mechanisms of device surface adhesion, biofilm accumulation, and reprogramming of host innate immune responses. We found that the S. aureus fibronectin binding protein A (FnBPA) is required for normal biofilm development in mammalian serum and that the SaeRS two-component system is required for functional FnBPA activity in serum. Furthermore, serum-developed biofilms deficient in FnBPA were mo...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Gries, C. M., Biddle, T., Bose, J. L., Kielian, T., Lo, D. D. Tags: Bacterial Infections Source Type: research

The Legionella pneumophila Metaeffector Lpg2505 (MesI) Regulates SidI-Mediated Translation Inhibition and Novel Glycosyl Hydrolase Activity [Molecular Pathogenesis]
Legionella pneumophila, the etiological agent of Legionnaires’ disease, employs an arsenal of hundreds of Dot/Icm-translocated effector proteins to facilitate replication within eukaryotic phagocytes. Several effectors, called metaeffectors, function to regulate the activity of other Dot/Icm-translocated effectors during infection. The metaeffector Lpg2505 is essential for L. pneumophila intracellular replication only when its cognate effector, SidI, is present. SidI is a cytotoxic effector that interacts with the host translation factor eEF1A and potently inhibits eukaryotic protein translation by an unknown mechani...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Joseph, A. M., Pohl, A. E., Ball, T. J., Abram, T. G., Johnson, D. K., Geisbrecht, B. V., Shames, S. R. Tags: Molecular Pathogenesis Source Type: research

Fluorescence-Reported Allelic Exchange Mutagenesis-Mediated Gene Deletion Indicates a Requirement for Chlamydia trachomatis Tarp during In Vivo Infectivity and Reveals a Specific Role for the C Terminus during Cellular Invasion [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The translocated actin recruiting phosphoprotein (Tarp) is a multidomain type III secreted effector used by Chlamydia trachomatis. In aggregate, existing data suggest a role of this effector in initiating new infections. As new genetic tools began to emerge to study chlamydial genes in vivo, we speculated as to what degree Tarp function contributes to Chlamydia’s ability to parasitize mammalian host cells. To address this question, we generated a complete tarP deletion mutant using the fluorescence-reported allelic exchange mutagenesis (FRAEM) technique and complemented the mutant in trans with wild-type tarP or muta...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Ghosh, S., Ruelke, E. A., Ferrell, J. C., Bodero, M. D., Fields, K. A., Jewett, T. J. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Paralogous Transcription Factors Stp1 and Stp2 of Candida albicans Have Distinct Functions in Nutrient Acquisition and Host Interaction [Molecular Pathogenesis]
Nutrient acquisition is a central challenge for all organisms. For the fungal pathogen Candida albicans, utilization of amino acids has been shown to be critical for survival, immune evasion, and escape, while the importance of catabolism of host-derived proteins and peptides in vivo is less well understood. Stp1 and Stp2 are paralogous transcription factors (TFs) regulated by the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing system and have been proposed to have distinct, if uncertain, roles in protein and amino acid utilization. We show here that Stp1 is required for proper utilization of peptides but has no effect on amino ac...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Miramon, P., Pountain, A. W., van Hoof, A., Lorenz, M. C. Tags: Molecular Pathogenesis Source Type: research

De Novo Purine Biosynthesis Is Required for Intracellular Growth of Staphylococcus aureus and for the Hypervirulence Phenotype of a purR Mutant [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Staphylococcus aureus is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in S. aureus, and mutations in purR result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype. ...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Goncheva, M. I., Flannagan, R. S., Heinrichs, D. E. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Chlamydia trachomatis Oligopeptide Transporter Performs Dual Functions of Oligopeptide Transport and Peptidoglycan Recycling [Molecular Pathogenesis]
Peptidoglycan, the sugar-amino acid polymer that composes the bacterial cell wall, requires a significant expenditure of energy to synthesize and is highly immunogenic. To minimize the loss of an energetically expensive metabolite and avoid host detection, bacteria often recycle their peptidoglycan, transporting its components back into the cytoplasm, where they can be used for subsequent rounds of new synthesis. The peptidoglycan-recycling substrate binding protein (SBP) MppA, which is responsible for recycling peptidoglycan fragments in Escherichia coli, has not been annotated for most intracellular pathogens. One such p...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Singh, R., Liechti, G., Slade, J. A., Maurelli, A. T. Tags: Molecular Pathogenesis Source Type: research

Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis [Microbial Immunity and Vaccines]
A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in m...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Wang, X., Singh, A. K., Zhang, X., Sun, W. Tags: Microbial Immunity and Vaccines Source Type: research

A Point Mutation in carR Is Involved in the Emergence of Polymyxin B-Sensitive Vibrio cholerae O1 El Tor Biotype by Influencing Gene Transcription [Bacterial Infections]
Antimicrobial peptides play an important role in host defense against Vibrio cholerae. Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strains has been reported in recent years, including in the devastating Yemen cholera outbreak during 2016-2018. To investigate the factor(s) responsible for the shift in the trend of sensitivity to PB, we studied the two-component system encoded by carRS, regulating the lipid A modification of El Tor vibrios, and...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Samanta, P., Mandal, R. S., Saha, R. N., Shaw, S., Ghosh, P., Dutta, S., Ghosh, A., Imamura, D., Morita, M., Ohnishi, M., Ramamurthy, T., Mukhopadhyay, A. K. Tags: Bacterial Infections Source Type: research

B Cells Inhibit CD4+ T Cell-Mediated Immunity to Brucella Infection in a Major Histocompatibility Complex Class II-Dependent Manner [Microbial Immunity and Vaccines]
Brucella spp. are facultative intracellular bacteria notorious for their ability to induce a chronic, and often lifelong, infection known as brucellosis. To date, no licensed vaccine exists for prevention of human disease, and mechanisms underlying chronic illness and immune evasion remain elusive. We and others have observed that B cell-deficient mice challenged with Brucella display reduced bacterial burden following infection, but the underlying mechanism has not been clearly defined. Here, we show that at 1 month postinfection, B cell deficiency alone enhanced resistance to splenic infection ~100-fold; however, combine...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Dadelahi, A. S., Lacey, C. A., Chambers, C. A., Ponzilacqua-Silva, B., Skyberg, J. A. Tags: Microbial Immunity and Vaccines Source Type: research

GABARAPL2 Is Critical for Growth Restriction of Toxoplasma gondii in HeLa Cells Treated with Gamma Interferon [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Gamma interferon (IFN-)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN- stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that -aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN--treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IF...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Zhang, Z., Gu, H., Li, Q., Zheng, J., Cao, S., Weng, C., Jia, H. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Differential Response of the Chicken Trachea to Chronic Infection with Virulent Mycoplasma gallisepticum Strain Ap3AS and Vaxsafe MG (Strain ts-304): a Transcriptional Profile [Host Response and Inflammation]
In this study, the transcriptional profiles of the trachea of unvaccinated chickens and chickens vaccinated with strain ts-304 were compared 2 weeks after challenge with M. gallisepticum strain Ap3AS during the chronic stage of infection. After challenge, genes, gene ontologies, pathways, and protein classes involved in inflammation, cytokine production and signaling, and cell proliferation were upregulated, while those involved in formation and motor movement of cilia, formation of intercellular junctional complexes, and formation of the cytoskeleton were downregulated in the unvaccinated birds compared to the vaccinated ...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Kulappu Arachchige, S. N., Young, N. D., Shil, P. K., Legione, A. R., Kanci Condello, A., Browning, G. F., Wawegama, N. K. Tags: Host Response and Inflammation Source Type: research

Porphyromonas gingivalis Cell Wall Components Induce Programmed Death Ligand 1 (PD-L1) Expression on Human Oral Carcinoma Cells by a Receptor-Interacting Protein Kinase 2 (RIP2)-Dependent Mechanism [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Programmed death-ligand 1 (PD-L1/B7-H1) serves as a cosignaling molecule in cell-mediated immune responses and contributes to chronicity of inflammation and the escape of tumor cells from immunosurveillance. Here, we investigated the molecular mechanisms leading to PD-L1 upregulation in human oral carcinoma cells and in primary human gingival keratinocytes in response to infection with Porphyromonas gingivalis (P. gingivalis), a keystone pathogen for the development of periodontitis. The bacterial cell wall component peptidoglycan uses bacterial outer membrane vesicles to be taken up by cells. Internalized peptidoglycan tr...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Groeger, S., Denter, F., Lochnit, G., Schmitz, M. L., Meyle, J. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Putative {beta}-Barrel Outer Membrane Proteins of the Bovine Digital Dermatitis-Associated Treponemes: Identification, Functional Characterization, and Immunogenicity [Microbial Immunity and Vaccines]
Bovine digital dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal etiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently sought. Using a reverse vaccinology approach, the present study surveyed the genomes of the three BDD-associated Treponema phylogroups for putative β-barrel outer membrane proteins and considered their potential as vaccine candidates. Selection criteria included the presence of a signal peptidase I cleavage s...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Staton, G. J., Carter, S. D., Ainsworth, S., Mullin, J., Smith, R. F., Evans, N. J. Tags: Microbial Immunity and Vaccines Source Type: research

Distinct Contributions of CD18 Integrins for Binding and Phagocytic Internalization of Pseudomonas aeruginosa [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Phagocytosis is the key mechanism for host control of Pseudomonas aeruginosa, a motile Gram-negative, opportunistic bacterial pathogen which frequently undergoes adaptation and selection for traits that are advantageous for survival. One such clinically relevant adaptation is the loss of bacterial motility, observed within chronic infections, that is associated with increased antibiotic tolerance and phagocytic resistance. Previous studies using phagocytes from a leukocyte adhesion deficiency type 1 (LAD-I) patient identified CD18 as a putative cell surface receptor for uptake of live P. aeruginosa. However, how bacterial ...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Demirdjian, S., Hopkins, D., Cumbal, N., Lefort, C. T., Berwin, B. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Tags: Masthead Source Type: research

Identification and Characterization of Staphylococcus delphini Internalization Pathway in Nonprofessional Phagocytic Cells [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The intracellular lifestyle of bacteria is widely acknowledged to be an important mechanism in chronic and recurring infection. Among the Staphylococcus genus, only Staphylococcus aureus and Staphylococcus pseudintermedius have been clearly identified as intracellular in nonprofessional phagocytic cells (NPPCs), for which the mechanism is mainly fibronectin-binding dependent. Here, we used bioinformatics tools to search for possible new fibronectin-binding proteins (FnBP-like) in other Staphylococcus species. We found a protein in Staphylococcus delphini called Staphylococcus delphini surface protein Y (SdsY). This protein...
Source: Infection and Immunity - April 20, 2020 Category: Infectious Diseases Authors: Maali, Y., Diot, A., Martins-Simoes, P., Bes, M., Bouvard, D., Vandenesch, F., Verhoeven, P. O., Laurent, F., Trouillet-Assant, S. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Structural and Biomolecular Analyses of Borrelia burgdorferi BmpD Reveal a Substrate-Binding Protein of an ABC-Type Nucleoside Transporter Family [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Borrelia burgdorferi sensu lato, the causative agent of tick-borne Lyme borreliosis (LB), has a limited metabolic capacity and needs to acquire nutrients, such as amino acids, fatty acids, and nucleic acids, from the host environment. Using X-ray crystallography, liquid chromatography-mass spectrometry, microscale thermophoresis, and cellular localization studies, we show that basic membrane protein D (BmpD) is a periplasmic substrate-binding protein of an ABC transporter system binding to purine nucleosides. Nucleosides are essential for bacterial survival in the host organism, and these studies suggest a key role for Bmp...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: Cuellar, J., Astrand, M., Elovaara, H., Pietikäinen, A., Siren, S., Liljeblad, A., Guedez, G., Salminen, T. A., Hytönen, J. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

TRIM32 Drives Pathogenesis in Streptococcal Toxic Shock-Like Syndrome and Streptococcus suis Meningitis by Regulating Innate Immune Responses [Host Response and Inflammation]
In this study, we showed that TRIM32 deficiency significantly reduced the level of bacteremia and the production of proinflammatory cytokines following severe S. suis infection, protecting infected mice from STSLS. The influence of TRIM32 gene deletion on a range of processes known to be involved in S. suis meningitis was also examined. Both levels of bacterial loads and indications of brain hemorrhage were reduced in infected Trim32–/– mice compared with infected wild-type (WT) controls. We also found that TRIM32 deficiency increased the permeability of the blood-brain barrier (BBB) and the recruitment of infl...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: OuYang, X., Guo, J., Lv, Q., Jiang, H., Zheng, Y., Liu, P., Zhao, T., Kong, D., Hao, H., Jiang, Y. Tags: Host Response and Inflammation Source Type: research

Neisseria meningitidis Induces Pathology-Associated Cellular and Molecular Changes in Trigeminal Schwann Cells [Bacterial Infections]
Neisseria meningitidis, a common cause of sepsis and bacterial meningitis, infects the meninges and central nervous system (CNS), primarily via paracellular traversal across the blood-brain barrier (BBB) or blood-cerebrospinal fluid barrier. N. meningitidis is often present asymptomatically in the nasopharynx, and the nerves extending between the nasal cavity and the brain constitute an alternative route by which the meningococci may reach the CNS. To date, the cellular mechanisms involved in nerve infection are not fully understood. Peripheral nerve glial cells are phagocytic and are capable of eliminating microorganisms,...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: Delbaz, A., Chen, M., Jen, F. E.- C., Schulz, B. L., Gorse, A.-D., Jennings, M. P., St John, J. A., Ekberg, J. A. K. Tags: Bacterial Infections Source Type: research

Streptococcus suis Serotype 2 Infection Causes Host Immunomodulation through Induction of Thymic Atrophy [Bacterial Infections]
Streptococcus suis serotype 2 is an important bacterial pathogen of swine and is also an emerging zoonotic agent that may be harmful to human health. Although the virulence genes of S. suis have been extensively studied, the mechanisms by which they damage the central immune organs have rarely been studied. In the current work, we wanted to uncover more details about the impact and mechanisms of S. suis on specific populations of thymic and immune cells in infected mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed that S. suis infection induced apoptosis in CD3...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: Wang, S., Lyu, C., Duan, G., Meng, F., Yang, Y., Yu, Y., He, X., Wang, Z., Gottschalk, M., Li, G., Cai, X., Wang, G. Tags: Bacterial Infections Source Type: research

Inhibition of tRNA Synthetases Induces Persistence in Chlamydia [Molecular Pathogenesis]
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections, and Chlamydia pneumoniae causes community-acquired respiratory infections. In vivo, the host immune system will release gamma interferon (IFN-) to combat infection. IFN- activates human cells to produce the tryptophan (Trp)-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Consequently, there is a reduction in cytosolic Trp in IFN--activated host cells. In evolving to obligate intracellular dependence, Chlamydia has significantly reduced its genome size and content, as it relies on the host cell for various nutrients. Importantly,...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: Hatch, N. D., Ouellette, S. P. Tags: Molecular Pathogenesis Source Type: research

Streptococcus pneumoniae Elaborates Persistent and Prolonged Competent State during Pneumonia-Derived Sepsis [Molecular Pathogenesis]
The competence regulon of pneumococcus regulates both genetic transformation and virulence. However, competence induction during host infection has not been examined. By using the serotype 2 strain D39, we transcriptionally fused the firefly luciferase (luc) to competence-specific genes and spatiotemporally monitored the competence development in a mouse model of pneumonia-derived sepsis. In contrast to the universally reported short transient burst of competent state in vitro, the naturally developed competent state was prolonged and persistent during pneumonia-derived sepsis. The competent state began at approximately 20...
Source: Infection and Immunity - March 23, 2020 Category: Infectious Diseases Authors: Lin, J., Park, P., Li, H., Oh, M. W., Dobrucki, I. T., Dobrucki, W., Lau, G. W. Tags: Molecular Pathogenesis Source Type: research