Combining Monophosphoryl Lipid A (MPL), CpG Oligodeoxynucleotide (ODN), and QS-21 Adjuvants Induces Strong and Persistent Functional Antibodies and T Cell Responses against Cell-Traversal Protein for Ookinetes and Sporozoites (CelTOS) of Plasmodium falciparum in BALB/c Mice [Fungal and Parasitic Infections]
Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an advanced vaccine candidate that has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts. As recombinant purified proteins are normally poor immunogens, they require to be admixed with an adjuvant(s); therefore, the objective of the present study was to evaluate the capacity of different vaccine adjuvants, monophosphoryl lipid A (MPL), CpG, and Quillaja saponaria Molina fraction 21 (QS-21), alone or in combination (MCQ [MPL/CpG/QS-21]), to enhance the immunogenicity of Escherichia coli-express...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Pirahmadi, S., Zakeri, S., Mehrizi, A. A., Djadid, N. D., Raz, A.-A., Sani, J. J. Tags: Fungal and Parasitic Infections Source Type: research

The NOD-scid IL2r{gamma}null Mouse Model Is Suitable for the Study of Osteoarticular Brucellosis and Vaccine Safety [Bacterial Infections]
Osteoarticular brucellosis is the most common complication in Brucella-infected humans regardless of age, sex, or immune status. The mechanism of bone destruction caused by Brucella species remained partially unknown due to the lack of a suitable animal model. Here, to study this complication, we explored the suitability of the use of the NOD-scid IL2rnull mouse to study osteoarticular brucellosis and examined the potential use of this strain to evaluate the safety of live attenuated vaccine candidates. Mice were inoculated intraperitoneally with a single dose of 1 x 104, 1 x 105, or 1 x 106 CFU of B. abortus S19 or the va...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Khalaf, O. H., Chaki, S. P., Garcia-Gonzalez, D. G., Ficht, T. A., Arenas-Gamboa, A. M. Tags: Bacterial Infections Source Type: research

Tracking of Borrelia afzelii Transmission from Infected Ixodes ricinus Nymphs to Mice [Bacterial Infections]
Quantitative and microscopic tracking of Borrelia afzelii transmission from infected Ixodes ricinus nymphs has shown a transmission cycle different from that of Borrelia burgdorferi and Ixodes scapularis. Borrelia afzelii organisms are abundant in the guts of unfed I. ricinus nymphs, and their numbers continuously decrease during feeding. Borrelia afzelii spirochetes are present in murine skin within 1 day of tick attachment. In contrast, spirochetes were not detectable in salivary glands at any stage of tick feeding. Further experiments demonstrated that tick saliva is not essential for B. afzelii infectivity, the most im...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Pospisilova, T., Urbanova, V., Hes, O., Kopacek, P., Hajdusek, O., Sima, R. Tags: Bacterial Infections Source Type: research

A Genomic Approach To Identify Klebsiella pneumoniae and Acinetobacter baumannii Strains with Enhanced Competitive Fitness in the Lungs during Multistrain Pneumonia [Bacterial Infections]
Microbial competition is most often studied at the genus or species level, but interstrain competition has been less thoroughly examined. Klebsiella pneumoniae is an important pathogen in the context of hospital-acquired pneumonia, and a better understanding of strain competition in the lungs could explain why some strains of this bacterium are more frequently isolated from pneumonia patients than others. We developed a barcode-free method called "StrainSeq" to simultaneously track the abundances of 10 K. pneumoniae strains in a murine pneumonia model. We demonstrate that one strain (KPPR1) repeatedly achieved a ...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Agard, M. J., Ozer, E. A., Morris, A. R., Piseaux, R., Hauser, A. R. Tags: Bacterial Infections Source Type: research

The Rate of CD4 T Cell Entry into the Lungs during Mycobacterium tuberculosis Infection Is Determined by Partial and Opposing Effects of Multiple Chemokine Receptors [Host Response and Inflammation]
The specific chemokine receptors utilized by Th1 cells to migrate into the lung during Mycobacterium tuberculosis infection are unknown. We previously showed in mice that CXCR3+ Th1 cells enter the lung parenchyma and suppress M. tuberculosis growth, while CX3CR1+ KLRG1+ Th1 cells accumulate in the lung vasculature and are nonprotective. Here we quantify the contributions of these chemokine receptors to the migration and entry rate of Th1 cells into M. tuberculosis-infected lungs using competitive adoptive transfer migration assays and mathematical modeling. We found that in 8.6 h half of M. tuberculosis-specific CD4 T cel...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Hoft, S. G., Sallin, M. A., Kauffman, K. D., Sakai, S., Ganusov, V. V., Barber, D. L. Tags: Host Response and Inflammation Source Type: research

Transmission-Blocking Vaccines: Old Friends and New Prospects [Minireviews]
In the progression of the life cycle of Plasmodium falciparum, a small proportion of asexual parasites differentiate into male or female sexual forms called gametocytes. Just like their asexual counterparts, gametocytes are contained within the infected host’s erythrocytes (RBCs). However, unlike their asexual partners, they do not exit the RBC until they are taken up in a blood meal by a mosquito. In the mosquito midgut, they are stimulated to emerge from the RBC, undergo fertilization, and ultimately produce tens of thousands of sporozoites that are infectious to humans. This transmission cycle can be blocked by an...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Acquah, F. K., Adjah, J., Williamson, K. C., Amoah, L. E. Tags: Minireviews Source Type: research

Epigenetic Changes Induced by Bacteroides fragilis Toxin [Molecular Genomics]
Enterotoxigenic Bacteroides fragilis (ETBF) is a Gram-negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of multiple intestinal neoplasia (Apcmin/+) mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have ...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Allen, J., Hao, S., Sears, C. L., Timp, W. Tags: Molecular Genomics Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Tags: Spotlight Source Type: research

Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia [Microbial Immunity and Vaccines]
Giardia lamblia, one of the most common protozoal infections of the human intestine, is an important worldwide cause of diarrheal disease, malabsorption, malnutrition, delayed cognitive development in children, and protracted postinfectious syndromes. Despite its medical importance, no human vaccine is available against giardiasis. A crude veterinary vaccine has been developed, and experimental vaccines based on expression of multiple variant-specific surface proteins have been reported, but poorly defined vaccine components and excessive antigen variability are problematic for pharmaceutical vaccine production. To expand ...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Davids, B. J., Liu, C. M., Hanson, E. M., Le, C. H. Y., Ang, J., Hanevik, K., Fischer, M., Radunovic, M., Langeland, N., Ferella, M., Svärd, S. G., Ghassemian, M., Miyamoto, Y., Eckmann, L. Tags: Microbial Immunity and Vaccines Source Type: research

Group A Streptococcus T Antigens Have a Highly Conserved Structure Concealed under a Heterogeneous Surface That Has Implications for Vaccine Design [Microbial Immunity and Vaccines]
In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Young, P. G., Raynes, J. M., Loh, J. M., Proft, T., Baker, E. N., Moreland, N. J. Tags: Microbial Immunity and Vaccines Source Type: research

Contribution of YjbIH to Virulence Factor Expression and Host Colonization in Staphylococcus aureus [Bacterial Infections]
To persist within the host and cause disease, Staphylococcus aureus relies on its ability to precisely fine-tune virulence factor expression in response to rapidly changing environments. During an unbiased transposon mutant screen, we observed that disruption of a two-gene operon, yjbIH, resulted in decreased levels of pigmentation and aureolysin (Aur) activity relative to the wild-type strain. Further analyses revealed that YjbH, a predicted thioredoxin-like oxidoreductase, is predominantly responsible for the observed yjbIH mutant phenotypes, though a minor role exists for the putative truncated hemoglobin YjbI. These di...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Austin, C. M., Garabaglu, S., Krute, C. N., Ridder, M. J., Seawell, N. A., Markiewicz, M. A., Boyd, J. M., Bose, J. L. Tags: Bacterial Infections Source Type: research

Study of Legionella Effector Domains Revealed Novel and Prevalent Phosphatidylinositol 3-Phosphate Binding Domains [Molecular Pathogenesis]
Legionella pneumophila and other Legionella species replicate intracellularly using the Icm/Dot type IV secretion system. In L. pneumophila this system translocates>300 effectors into host cells and in the Legionella genus thousands of effectors were identified, the function of most of which is unknown. Fourteen L. pneumophila effectors were previously shown to specifically bind phosphoinositides (PIs) using dedicated domains. We found that PI-binding domains of effectors are usually not homologous to one another; they are relatively small and located at the effectors' C termini. We used the previously identified Legion...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Nachmias, N., Zusman, T., Segal, G. Tags: Molecular Pathogenesis Source Type: research

The Second Messenger c-di-AMP Regulates Diverse Cellular Pathways Involved in Stress Response, Biofilm Formation, Cell Wall Homeostasis, SpeB Expression, and Virulence in Streptococcus pyogenes [Molecular Pathogenesis]
Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. The cellular level of c-di-AMP in Streptococcus pyogenes is predicted to be controlled by the synthase DacA and two putative phosphodiesterases, GdpP and Pde2. To investigate the role of c-di-AMP in S. pyogenes, we generated null mutants in each of these proteins by gene deletion. Unlike those in other Gram-positive pathogens such as Staphylococcus aureus and Listeria monocytogenes, DacA in S. pyogenes was not essential for growth in rich media. The DacA null mutant presented a growth defect that manifested through an increased lag time, produc...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Fahmi, T., Faozia, S., Port, G. C., Cho, K. H. Tags: Molecular Pathogenesis Source Type: research

Prediction and Validation of Immunogenic Domains of Pneumococcal Proteins Recognized by Human CD4+ T Cells [Microbial Immunity and Vaccines]
CD4+ T-cell mechanisms are implied in protection against pneumococcal colonization; however, their target antigens and function are not well defined. In contrast to high-throughput protein arrays for serology, basic antigen tools for CD4+ T-cell studies are lacking. Here, we evaluate the potential of a bioinformatics tool for in silico prediction of immunogenicity as a method to reveal domains of pneumococcal proteins targeted by human CD4+ T cells. For 100 pneumococcal proteins, CD4+ T-cell immunogenicity was predicted based on HLA-DRB1 binding motifs. For 20 potentially CD4+ T-cell immunogenic proteins, epitope regions w...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: van de Garde, M. D. B., van Westen, E., Poelen, M. C. M., Rots, N. Y., van Els, C. A. C. M. Tags: Microbial Immunity and Vaccines Source Type: research

Bacteriophage Resistance Alters Antibiotic-Mediated Intestinal Expansion of Enterococci [Host-Associated Microbial Communities]
This study demonstrates that phage therapy could be used in combination with antibiotics to target enterococci within a dysbiotic microbiota. Enterococci that evade phage therapy by developing resistance may be less fit at colonizing the intestine and sensitized to vancomycin, preventing their overgrowth during antibiotic treatment. (Source: Infection and Immunity)
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Chatterjee, A., Johnson, C. N., Luong, P., Hullahalli, K., McBride, S. W., Schubert, A. M., Palmer, K. L., Carlson, P. E., Duerkop, B. A. Tags: Host-Associated Microbial Communities Source Type: research

Low-Level Parasite Persistence Drives Vasculitis and Myositis in Skeletal Muscle of Mice Chronically Infected with Trypanosoma cruzi [Host Response and Inflammation]
In chronic Trypanosoma cruzi infection, the cause of Chagas disease, life-threatening inflammatory diseases develop over time in the heart, esophagus, and colon of some patients. C57BL/6 mice infected with the myotropic Colombiana strain of T. cruzi model many of the immunological and parasitological features of human infection but succumb to chronic paralyzing myositis and skeletal muscle vasculitis, not cardiomyopathy or gastrointestinal disease. Here we show that T cell depletion in the chronic phase of this model increased tissue parasitism to acute-phase levels and induced neutrophilic skeletal muscle inflammation. Co...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Weaver, J. D., Hoffman, V. J., Roffe, E., Murphy, P. M. Tags: Host Response and Inflammation Source Type: research

Pathogenic Mannheimia haemolytica Invades Differentiated Bovine Airway Epithelial Cells [Bacterial Infections]
The Gram-negative bacterium Mannheimia haemolytica is the primary bacterial species associated with bovine respiratory disease (BRD) and is responsible for significant economic losses to livestock industries worldwide. Healthy cattle are frequently colonized by commensal serotype A2 strains, but disease is usually caused by pathogenic strains of serotype A1. For reasons that are poorly understood, a transition occurs within the respiratory tract and a sudden explosive proliferation of serotype A1 bacteria leads to the onset of pneumonic disease. Very little is known about the interactions of M. haemolytica with airway epit...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Cozens, D., Sutherland, E., Lauder, M., Taylor, G., Berry, C. C., Davies, R. L. Tags: Bacterial Infections Source Type: research

Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation [Molecular Pathogenesis]
Although nontypeable Haemophilus influenzae (NTHi) is a human-specific nasopharyngeal commensal bacterium, it also causes upper respiratory tract infections in children and lower respiratory tract infections in the elderly, resulting in frequent antibiotic use. The transition from symbiotic colonizing bacterium to opportunistic pathogen is not completely understood. Incorporation of sialic acids into lipooligosaccharides is thought to play an important role in bacterial virulence. It has been known for more than 25 years that sialic acids increase resistance to complement-mediated killing; however, the mechanism of action ...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Oerlemans, M. M. P., Moons, S. J., Heming, J. J. A., Boltje, T. J., de Jonge, M. I., Langereis, J. D. Tags: Molecular Pathogenesis Source Type: research

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span [Host-Associated Microbial Communities]
This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Kirakodu, S., Chen, J., Gonzalez Martinez, J., Gonzalez, O. A., Ebersole, J. Tags: Host-Associated Microbial Communities Source Type: research

Antigen-Specific CD4+ T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for Clearing Chlamydia from the Small Intestine but Not the Large Intestine [Bacterial Infections]
The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in ~4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in α/β T cells o...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Lin, H., He, C., Koprivsek, J. J., Chen, J., Zhou, Z., Arulanandam, B., Xu, Z., Tang, L., Zhong, G. Tags: Bacterial Infections Source Type: research

Suppression of Obesity by an Intestinal Helminth through Interactions with Intestinal Microbiota [Host Response and Inflammation]
Obesity is increasingly causing lifestyle diseases in developed countries where helminthic infections are rarely seen. Here, we investigated whether an intestinal nematode, Heligmosomoides polygyrus, has a suppressive role in diet-induced obesity in mice. Infection with H. polygyrus suppressed weight gain in obese mice, which was associated with increased uncoupling protein 1 (UCP1) expression in adipocytes and a higher serum norepinephrine (NE) concentration. Blocking interactions of NE with its receptor on adipocytes resulted in the failure to prevent weight gain and to enhance UCP1 expression in obese mice infected with...
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Authors: Shimokawa, C., Obi, S., Shibata, M., Olia, A., Imai, T., Suzue, K., Hisaeda, H. Tags: Host Response and Inflammation Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 21, 2019 Category: Infectious Diseases Tags: Masthead Source Type: research

Borrelia burgdorferi bbk13 Is Critical for Spirochete Population Expansion in the Skin during Early Infection [Bacterial Infections]
Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted via the bite of an infected tick. B. burgdorferi enters the skin, disseminates via the bloodstream, and infects various distal tissues, leading to inflammatory sequelae, such as Lyme arthritis and Lyme carditis. B. burgdorferi linear plasmid 36 (lp36) is critical for mammalian infectivity; however, the full complement of genes on lp36 that contribute to this process remains unknown. Through a targeted mutagenesis screen of the genes on lp36, we identified a novel infectivity gene of unknown function, bbk13, which encodes an immunogenic, non-su...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Aranjuez, G. F., Kuhn, H. W., Adams, P. P., Jewett, M. W. Tags: Bacterial Infections Source Type: research

Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1 [Molecular Pathogenesis]
Gastrointestinal (GI) colonization of 2-day-old (P2) rat pups with Escherichia coli K1 results in translocation of the colonizing bacteria across the small intestine, bacteremia, and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection, but not colonization, is strongly age dependent; pups become progressively less susceptible to infection over the P2-to-P9 period. Colonization leads to strong downregulation of the gene encoding trefoil factor 2 (Tff2), preventing maturation of the protective mucus barrier in the small intestine. Trefoil factors promote mucosal homeostasis. We investi...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: McCarthy, A. J., Birchenough, G. M. H., Taylor, P. W. Tags: Molecular Pathogenesis Source Type: research

Sortase-Dependent Proteins Promote Gastrointestinal Colonization by Enterococci [Host-Associated Microbial Communities]
The human gastrointestinal tract (GIT) is inhabited by a dense microbial community of symbionts. Enterococci are among the earliest members of this community and remain core members of the GIT microbiota throughout life. Enterococci have also recently emerged as opportunistic pathogens and major causes of nosocomial infections. Although recognized as a prerequisite for infection, colonization of the GIT by enterococci remains poorly understood. One way that bacteria adapt to dynamic ecosystems like the GIT is through the use of their surface proteins to sense and interact with components of their immediate environment. In ...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Banla, L. I., Pickrum, A. M., Hayward, M., Kristich, C. J., Salzman, N. H. Tags: Host-Associated Microbial Communities Source Type: research

The Plasmid-Encoded pGP3 Promotes Chlamydia Evasion of Acidic Barriers in Both Stomach and Vagina [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Although Chlamydia trachomatis is a human genital tract pathogen, chlamydial organisms have frequently been detected in both vaginal and rectal swab samples of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for Chlamydia muridarum to colonize the mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization ability of a pGP3-deficient C. muridarum mutant, suggesting that pGP3 is required for C. muridarum to reach but not to colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 10...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Zhang, T., Huo, Z., Ma, J., He, C., Zhong, G. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Arcanobacterium haemolyticum Utilizes Both Phospholipase D and Arcanolysin To Mediate Its Uptake into Nonphagocytic Cells [Molecular Pathogenesis]
Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis and wound infections. A few studies have suggested that A. haemolyticum is able to induce its uptake into nonphagocytic epithelial cells, but the bacterial factors associated with host cell invasion and the host cell processes involved have yet to be studied. We investigated how two A. haemolyticum virulence factors, arcanolysin (ALN) and phospholipase D (PLD), affect the ability of the bacteria to adhere to and subsequently invade Detroit 562 pharyngeal epithelial cells. The sphingomyelinase activity of phospholipase D was necessary to incr...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Gellings, P. S., McGee, D. J. Tags: Molecular Pathogenesis Source Type: research

Differential Recognition of Vibrio parahaemolyticus OmpU by Toll-Like Receptors in Monocytes and Macrophages for the Induction of Proinflammatory Responses [Host Response and Inflammation]
In this study, in an effort towards characterizing the effect of VpOmpU on innate immune responses of the host, we observed that VpOmpU is recognized by the Toll-like receptor 1/2 (TLR1/2) heterodimer in THP-1 monocytes but by both TLR1/2 and TLR2/6 heterodimers in RAW 264.7 macrophages. To the best of our knowledge, this is the first report of a natural pathogen-associated molecular pattern (PAMP) recognized by both TLR1/2 and TLR2/6 heterodimers; so far, mainly the synthetic ligand Pam2CSK4 has been known to be recognized by both the TLR1/2 and TLR2/6 heterodimers. We also have shown that VpOmpU can activate monocytes an...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Gulati, A., Kumar, R., Mukhopadhaya, A. Tags: Host Response and Inflammation Source Type: research

Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells [Fungal and Parasitic Infections]
In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12 and 20 h after in vitro infection, prior to egress. We induced silencing of SUB1 (SUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease in the proportion of released merozoites in vitro (P
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Nava, S., White, A. C., Castellanos-Gonzalez, A. Tags: Fungal and Parasitic Infections Source Type: research

Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 by Enhancing Its Clearance in the Airways [Host Response and Inflammation]
In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of monocyte-myeloid-derived suppressor cells (M-MDSCs) and neutrophils that actively produce IL-10. However, M-MDSCs were the cells that sustained the production of IL-10 over the time of infection evaluated. Using mice unable to produce IL-10 (IL-10–/–), we observed that...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Penaloza, H. F., Noguera, L. P., Ahn, D., Vallejos, O. P., Castellanos, R. M., Vazquez, Y., Salazar-Echegarai, F. J., Gonzalez, L., Suazo, I., Pardo-Roa, C., Salazar, G. A., Prince, A., Bueno, S. M. Tags: Host Response and Inflammation Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Tags: Spotlight Source Type: research

Dual Gene Expression Analysis Identifies Factors Associated with Staphylococcus aureus Virulence in Diabetic Mice [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus being a major complication of diabetic wound infections. We investigated how the diabetic environment influences S. aureus skin infection and observed an increased susceptibility to infection in mouse models of both type I and type II diabetes. A dual gene expression approach was taken to investigate transcriptional alterations in both the host and bacterium after infection. While analysis of the host response revealed only minor changes between infected control and diabetic mice, we observed that S. aureus is...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Jacquet, R., LaBauve, A. E., Akoolo, L., Patel, S., Alqarzaee, A. A., Wong Fok Lung, T., Poorey, K., Stinear, T. P., Thomas, V. C., Meagher, R. J., Parker, D. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia). Both diseases are linked to the transmission of human immunodeficiency virus (HIV) and preterm birth, which complications are likely to result from the disruption of the cervicovaginal epithelial barrier. Here, we show that paracellular permeability of...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Hinderfeld, A. S., Phukan, N., Bär, A.-K., Roberton, A. M., Simoes-Barbosa, A. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Yersinia pestis Pla Protein Thwarts T Cell Defense against Plague [Host Response and Inflammation]
This study demonstrated that the Y. pestis plasminogen activator Pla, a protease that promotes fibrin degradation, thwarts T cell-mediated defense against fully virulent Y. pestis. Introducing a single point mutation into the active site of Pla suffices to render fully virulent Y. pestis susceptible to primed T cells. Mechanistic studies revealed essential roles for fibrin during T cell-mediated defense against Pla-mutant Y. pestis. Moreover, the efficacy of T cell-mediated protection against various Y. pestis strains displayed an inverse relationship with their levels of Pla activity. Together, these data indicate that Pl...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Smiley, S. T., Szaba, F. M., Kummer, L. W., Duso, D. K., Lin, J.-S. Tags: Host Response and Inflammation Source Type: research

Alternative Enzyme Protection Assay To Overcome the Drawbacks of the Gentamicin Protection Assay for Measuring Entry and Intracellular Survival of Staphylococci [Bacterial Infections]
Precise enumeration of living intracellular bacteria is the key step to estimate the invasion potential of pathogens and host immune responses to understand the mechanism and kinetics of bacterial pathogenesis. Therefore, quantitative assessment of host-pathogen interactions is essential for development of novel antibacterial therapeutics for infectious disease. The gentamicin protection assay (GPA) is the most widely used method for these estimations by counting the CFU of intracellular living pathogens. Here, we assess the longstanding drawbacks of the GPA by employing an antistaphylococcal endopeptidase as a bactericida...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Kim, J.-H., Chaurasia, A. K., Batool, N., Ko, K. S., Kim, K. K. Tags: Bacterial Infections Source Type: research

Neutrophils Dampen Adaptive Immunity in Brucellosis [Host Response and Inflammation]
Brucella organisms are intracellular stealth pathogens of animals and humans. The bacteria overcome the assault of innate immunity at early stages of an infection. Removal of polymorphonuclear neutrophils (PMNs) at the onset of adaptive immunity against Brucella abortus favored bacterial elimination in mice. This was associated with higher levels of interferon gamma (IFN-) and a higher proportion of cells expressing interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), compatible with M1 macrophages, in PMN-depleted B. abortus-infected (PMNd-Br) mice. At later times in the acute infection phase, the amounts of I...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Mora-Cartin, R., Gutierrez-Jimenez, C., Alfaro-Alarcon, A., Chaves-Olarte, E., Chacon-Diaz, C., Barquero-Calvo, E., Moreno, E. Tags: Host Response and Inflammation Source Type: research

Interferon Lambda Inhibits Bacterial Uptake during Influenza Superinfection [Host Response and Inflammation]
Influenza kills 30,000 to 40,000 people each year in the United States and causes 10 times as many hospitalizations. A common complication of influenza is bacterial superinfection, which exacerbates morbidity and mortality from the viral illness. Recently, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as the dominant pathogen found in bacterial superinfection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial superinfection. Current therapy for influenza/bacterial superinfection consists of treating the underlying influenza infection and adding various anti...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Rich, H. E., McCourt, C. C., Zheng, W. Q., McHugh, K. J., Robinson, K. M., Wang, J., Alcorn, J. F. Tags: Host Response and Inflammation Source Type: research

Analysis of Invasive Nontypeable Haemophilus influenzae Isolates Reveals Selection for the Expression State of Particular Phase-Variable Lipooligosaccharide Biosynthetic Genes [Molecular Pathogenesis]
In this study, we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF shows a correlation with invasive NTHi isolates. We hypothesize that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance and may serve as a marker for invasive NTHi. (Source: Infection and Immunity)
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Phillips, Z. N., Brizuela, C., Jennison, A. V., Staples, M., Grimwood, K., Seib, K. L., Jennings, M. P., Atack, J. M. Tags: Molecular Pathogenesis Source Type: research

Leishmania donovani Lipophosphoglycan Increases Macrophage-Dependent Chemotaxis of CXCR6-Expressing Cells via CXCL16 Induction [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
CXCL16 is a multifunctional chemokine that is highly expressed by macrophages and other immune cells in response to bacterial and viral pathogens; however, little is known regarding the role of CXCL16 during parasitic infections. The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. Even though chemokine production is a host defense mechanism during infection, subversion of the host chemokine system constitutes a survival strategy adopted by the parasite. Here, we report that L. donovani promastigotes upregulate CXCL16 synthesis and secretion by bone marrow-derived macrophages (BMDM)....
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Chaparro, V., Leroux, L.-P., Zimmermann, A., Jardim, A., Johnston, B., Descoteaux, A., Jaramillo, M. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Mouse Inhalation Model of Cryptococcus neoformans Infection Recapitulates Strain Virulence in Humans and Shows that Closely Related Strains Can Possess Differential Virulence [Fungal and Parasitic Infections]
In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with Cryptococcus neoformans strains with the same multilocus sequence type (MLST). Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome was not associated with the patient CD4 count. Patient mortality was associated with higher cryptococcal antigen levels, the cerebrospinal fluid (CSF) fungal burden by quantitative culture, and low CSF fungal clearance. The virulence of a subset of clinical strains with the same sequence type was analyzed using...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Mukaremera, L., McDonald, T. R., Nielsen, J. N., Molenaar, C. J., Akampurira, A., Schutz, C., Taseera, K., Muzoora, C., Meintjes, G., Meya, D. B., Boulware, D. R., Nielsen, K. Tags: Fungal and Parasitic Infections Source Type: research

Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine [Fungal and Parasitic Infections]
Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory ...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Rollins-Smith, L. A., Ruzzini, A. C., Fites, J. S., Reinert, L. K., Hall, E. M., Joosse, B. A., Ravikumar, V. I., Huebner, M. I., Aka, A., Kehs, M. H., Gillard, B. M., Doe, E., Tasca, J. A., Umile, T. P., Clardy, J., Minbiole, K. P. C. Tags: Fungal and Parasitic Infections Source Type: research

A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during Acinetobacter baumannii Infection [Host Response and Inflammation]
Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protec...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Choby, J. E., Monteith, A. J., Himmel, L. E., Margaritis, P., Shirey-Rice, J. K., Pruijssers, A., Jerome, R. N., Pulley, J., Skaar, E. P. Tags: Host Response and Inflammation Source Type: research

Characterization of Early Stages of Human Alveolar Infection by the Q Fever Agent Coxiella burnetii [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In this study, we investigated the interaction between C. burnetii and other pulmonary cell types apart from the lung environment. C. burnetii formed a prototypical PV and replicated efficiently in human pulmonary fibroblasts and in airway, but not alveolar, epithelial cells. Atypical PV expansion in alveolar epithelial cells was attributed in part to defective recruitment of autophagy-related proteins. Further assessment of the C. burnetii growth niche showed that macrophages mounted a robust interleukin 8 (IL-8), neutrophil-attracting response to C. burnetii and ultimately shifted to an M2-polarized phenotype characteris...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Dragan, A. L., Kurten, R. C., Voth, D. E. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Transcriptional Analysis Shows a Robust Host Response to Toxoplasma gondii during Early and Late Chronic Infection in Both Male and Female Mice [Host Response and Inflammation]
The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased at 6 months postinfection for both male and female mice. While m...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Garfoot, A. L., Cervantes, P. W., Knoll, L. J. Tags: Host Response and Inflammation Source Type: research

Control of Staphylococcus aureus Quorum Sensing by a Membrane-Embedded Peptidase [Molecular Pathogenesis]
Gram-positive bacteria process and release small peptides, or pheromones, that act as signals for the induction of adaptive traits, including those involved in pathogenesis. One class of small signaling pheromones is the cyclic autoinducing peptides (AIPs), which regulate expression of genes that orchestrate virulence and persistence in a range of microbes, including staphylococci, listeriae, clostridia, and enterococci. In a genetic screen for Staphylococcus aureus secreted virulence factors, we identified an S. aureus mutant containing an insertion in the gene SAUSA300_1984 (mroQ), which encodes a putative membrane-embed...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Cosgriff, C. J., White, C. R., Teoh, W. P., Grayczyk, J. P., Alonzo, F. Tags: Molecular Pathogenesis Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Tags: Masthead Source Type: research

Dietary Chitin Particles Called Mimetic Fungi Ameliorate Colitis in Toll-Like Receptor 2/CD14- and Sex-Dependent Manners [Host Response and Inflammation]
Chitin is a natural N-acetylglucosamine polymer and a major structural component of fungal cell walls. Dietary chitin is mucoadhesive; anti-inflammatory effects of chitin microparticles (CMPs; 1- to 10-μm diameters) have been demonstrated in models of inflammatory bowel disease (IBD). The goals of this study were to assess (i) whether CMPs among various chitin preparations are the most effective against colitis in male and female mice and (ii) whether host chitin-binding Toll-like receptor 2 (TLR2) and CD14 are required for the anti-inflammatory effect of chitin. We found that colitis in male mice was ameliorated by CMP...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Louis, P., Mercer, B., Cirone, A. M., Johnston, C., Lee, Z. J., Esiobu, N., Li, Z., Wei, J., Dorey, C. K., Shibata, Y., Nan, C. Tags: Host Response and Inflammation Source Type: research

MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity [Molecular Pathogenesis]
Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in Staphylococcus aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant, we observed a drastic reduction in proteolysis, hemolysis, and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII an...
Source: Infection and Immunity - April 23, 2019 Category: Infectious Diseases Authors: Marroquin, S., Gimza, B., Tomlinson, B., Stein, M., Frey, A., Keogh, R. A., Zapf, R., Todd, D. A., Cech, N. B., Carroll, R. K., Shaw, L. N. Tags: Molecular Pathogenesis Source Type: research

Immunological Responses to the Relapsing Fever Spirochete Borrelia turicatae in Infected Rhesus Macaques: Implications for Pathogenesis and Diagnosis [Host Response and Inflammation]
The global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with Borrelia turicatae (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody response...
Source: Infection and Immunity - March 25, 2019 Category: Infectious Diseases Authors: Embers, M. E., Krishnavajhala, A., Armstrong, B. A., Curtis, M. W., Pahar, B., Wilder, H. K., Allen, M. S., Beare, P. A., Hasenkampf, N. R., Lopez, J. E. Tags: Host Response and Inflammation Source Type: research

Redundant and Distinct Roles of Secreted Protein Eap and Cell Wall-Anchored Protein SasG in Biofilm Formation and Pathogenicity of Staphylococcus aureus [Bacterial Infections]
Chronic and fatal infections caused by Staphylococcus aureus are sometimes associated with biofilm formation. Secreted proteins and cell wall-anchored proteins (CWAPs) are important for the development of polysaccharide-independent biofilms, but functional relationships between these proteins are unclear. In the present study, we report the roles of the extracellular adherence protein Eap and the surface CWAP SasG in S. aureus MR23, a clinical methicillin-resistant isolate that forms a robust protein-dependent biofilm and accumulates a large amount of Eap in the extracellular matrix. Double deletion of eap and sasG, but no...
Source: Infection and Immunity - March 25, 2019 Category: Infectious Diseases Authors: Yonemoto, K., Chiba, A., Sugimoto, S., Sato, C., Saito, M., Kinjo, Y., Marumo, K., Mizunoe, Y. Tags: Bacterial Infections Source Type: research