The Great ESKAPE: Exploring the Crossroads of Bile and Antibiotic Resistance in Bacterial Pathogens [Minireviews]
Throughout the course of infection, many pathogens encounter bactericidal conditions that threaten the viability of the bacteria and impede the establishment of infection. Bile is one of the most innately bactericidal compounds present in humans, functioning to reduce the bacterial burden in the gastrointestinal tract while also aiding in digestion. It is becoming increasingly apparent that pathogens successfully resist the bactericidal conditions of bile, including bacteria that do not normally cause gastrointestinal infections. This review highlights the ability of Enterococcus, Staphylococcus, Klebsiella, Acinetobacter,...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Gipson, K. S., Nickerson, K. P., Drenkard, E., Llanos-Chea, A., Dogiparthi, S. K., Lanter, B. B., Hibbler, R. M., Yonker, L. M., Hurley, B. P., Faherty, C. S. Tags: Minireviews Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Tags: Spotlight Source Type: research

Paracellular Pathway-Mediated Mycoplasma hyopneumoniae Migration across Porcine Airway Epithelial Barrier under Air-Liquid Interface Conditions [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In this study, we established air-liquid interface culture systems for pig bronchial epithelial cells (ALI-PBECs) that were comparable to the conditions in the native bronchus in vivo. We used this ALI-PBECs model to study the infection and migration characteristics of M. hyopneumoniae in vitro. Based on the results, we confirmed that M. hyopneumoniae was able to adhere to ALI-PBECs and disrupt mucociliary function. Importantly, M. hyopneumoniae could migrate to the basolateral chamber through the paracellular route but not the transcellular pathway, and this was achieved by reversibly disrupting tight junctions (TJs) and ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Wang, H., Zhang, Z., Xie, X., Liu, B., Wei, Y., Gan, Y., Yuan, T., Ni, B., Wang, J., Zhang, L., Xiong, Q., Shao, G., Feng, Z. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System [Bacterial Infections]
Streptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors are known to contribute to persistent colonization of this niche, and many are important in mucosal immunity and vaccine development. In this work, mice were infected intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in sequenced isolates of S. pyogenes. Deletion of the QS system’s transcriptional activator (rgg2) dramatically diminished the percentage of colonized mice, while deletion of the transcriptio...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Gogos, A., Federle, M. J. Tags: Bacterial Infections Source Type: research

Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the Netherlands [Molecular Pathogenesis]
In this study, we determined the relationship between binding of IgG or IgM and the bacterial survival in normal human serum for 267 invasive H. influenzae strains from Spain, Portugal, and the Netherlands, of which the majority (200 [75%]) were NTHi. NTHi bacteria opsonized with high levels of IgM had the lowest survival in human serum. IgM binding to the bacterial surface, but not IgG binding, was shown to be associated with complement-mediated killing of NTHi strains. We conclude that evasion of IgM binding by NTHi strains increases survival in blood, thereby potentially contributing to their ability to cause severe inv...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Dudukina, E., de Smit, L., Verhagen, G. J. A., van de Ende, A., Marimon, J. M., Bajanca-Lavado, P., Ardanuy, C., Marti, S., de Jonge, M. I., Langereis, J. D. Tags: Molecular Pathogenesis Source Type: research

The ASM Journals Committee Values the Contributions of Black Microbiologists [Editorial]
(Source: Infection and Immunity)
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Schloss, P. D., Junior, M., Alvania, R., Arias, C. A., Baumler, A., Casadevall, A., Detweiler, C., Drake, H., Gilbert, J., Imperiale, M. J., Lovett, S., Maloy, S., McAdam, A. J., Newton, I. L. G., Sadowsky, M. J., Sandri-Goldin, R. M., Silhavy, T. J., Ton Tags: Editorial Source Type: research

Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia [Host Response and Inflammation]
We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts (n = 214). Antibody avidity was investigated. Bacteremic patient sera (n = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli, respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI I...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Theprungsirikul, J., Thaden, J. T., Wierzbicki, R. M., Burns, A. S., Skopelja-Gardner, S., Fowler, V. G., Winthrop, K. L., Martin, I. W., Rigby, W. F. C. Tags: Host Response and Inflammation Source Type: research

Importance of the Immunodominant CD8+ T Cell Epitope of Plasmodium berghei Circumsporozoite Protein in Parasite- and Vaccine-Induced Protection [Fungal and Parasitic Infections]
In this study, we characterized the importance of the immunodominant CSP-derived epitope SYIPSAEKI of Plasmodium berghei in both sporozoite- and vaccine-induced protection in murine infection models. In BALB/c mice, where SYIPSAEKI is efficiently presented in the context of the major histocompatibility complex class I (MHC-I) molecule H-2-Kd, we established that epitope-specific CD8+ T cell responses contribute to parasite killing following sporozoite immunization. Yet, sterile protection was achieved in the absence of this epitope, substantiating the concept that other antigens can be sufficient for parasite-induced prote...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Gibbins, M. P., Müller, K., Glover, M., Liu, J., Putrianti, E. D., Bauza, K., Reyes-Sandoval, A., Matuschewski, K., Silvie, O., Hafalla, J. C. R. Tags: Fungal and Parasitic Infections Source Type: research

Comparative Study of Immunogenic Properties of Purified Capsular Polysaccharides from Streptococcus suis Serotypes 3, 7, 8, and 9: the Serotype 3 Polysaccharide Induces an Opsonizing IgG Response [Microbial Immunity and Vaccines]
This study provides important information on the divergent evolution of CPS serotypes with highly different structural and/or biochemical properties within S. suis and their interaction with the immune system. (Source: Infection and Immunity)
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Goyette-Desjardins, G., Auger, J.-P., Dolbec, D., Vinogradov, E., Okura, M., Takamatsu, D., Van Calsteren, M.-R., Gottschalk, M., Segura, M. Tags: Microbial Immunity and Vaccines Source Type: research

Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms [Bacterial Infections]
This study describes key aspects of the interaction between primary human neutrophils and S. aureus biofilms and provides insight into how S. aureus evades the neutrophil response to cause persistent infections. (Source: Infection and Immunity)
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Bhattacharya, M., Berends, E. T. M., Zheng, X., Hill, P. J., Chan, R., Torres, V. J., Wozniak, D. J. Tags: Bacterial Infections Source Type: research

Genome-Wide Assessment of Streptococcus agalactiae Genes Required for Survival in Human Whole Blood and Plasma [Bacterial Infections]
Streptococcus agalactiae (group B streptococcus, or GBS) is a common cause of bacteremia and sepsis in newborns, pregnant women, and immunocompromised patients. The molecular mechanisms used by GBS to survive and proliferate in blood are not well understood. Here, using a highly virulent GBS strain and transposon-directed insertion site sequencing (TraDIS), we performed genome-wide screens to discover novel GBS genes required for bacterial survival in human whole blood and plasma. The screen identified 85 and 41 genes that are required for GBS growth in whole blood and plasma, respectively. A common set of 29 genes was req...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Zhu, L., Yerramilli, P., Pruitt, L., Ojeda Saavedra, M., Cantu, C. C., Olsen, R. J., Beres, S. B., Waller, A. S., Musser, J. M. Tags: Bacterial Infections Source Type: research

Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling through the Interleukin-1 Receptor [Host Response and Inflammation]
Group A Streptococcus (GAS) is the etiologic agent of numerous high-morbidity and high-mortality diseases. Infections are typically highly proinflammatory. During the invasive infection necrotizing fasciitis, this is in part due to the GAS protease SpeB directly activating interleukin-1β (IL-1β) independent of the canonical inflammasome pathway. The upper respiratory tract is the primary site for GAS colonization, infection, and transmission, but the host-pathogen interactions at this site are still largely unknown. We found that in the murine nasopharynx, SpeB enhanced IL-1β-mediated inflammation and the ch...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: LaRock, D. L., Russell, R., Johnson, A. F., Wilde, S., LaRock, C. N. Tags: Host Response and Inflammation Source Type: research

Differential Induction of Type I and III Interferons by Staphylococcus aureus [Host Response and Inflammation]
In this study, we screened 75 S. aureus strains for their ability to induce type I and III IFN. Both cytokine pathways were differentially stimulated by various S. aureus strains independently of their isolation sites or methicillin resistance profiles. These induction patterns persisted over time, and type I and III IFN generation differentially correlated with tumor necrosis factor alpha production. Investigation of one isolate, strain 126, showed a significant defect in type I IFN induction that persisted over several time points. The lack of induction was not due to differential phagocytosis, subcellular location, or c...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Peignier, A., Planet, P. J., Parker, D. Tags: Host Response and Inflammation Source Type: research

Characterization of Extracellular Vesicles from Entamoeba histolytica Identifies Roles in Intercellular Communication That Regulates Parasite Growth and Development [Fungal and Parasitic Infections]
Extracellular vesicles (EVs) secreted by eukaryotic and prokaryotic cells to transport lipids, proteins, and nucleic acids to the external environment have important roles in cell-cell communication through cargo transfer. We identified and characterized EVs from Entamoeba histolytica, a protozoan parasite and a human pathogen. Conditioned medium from amebic parasites contained particles consistent with the expected size and morphology of EVs. Mass spectrometry was used to characterize the EV proteome and showed that it was enriched in common exosome marker proteins, including proteins associated with vesicle formation, ce...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Sharma, M., Morgado, P., Zhang, H., Ehrenkaufer, G., Manna, D., Singh, U. Tags: Fungal and Parasitic Infections Source Type: research

Phosphotransferase System Uptake and Metabolism of the {beta}-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue Infection [Molecular Pathogenesis]
Streptococcus pyogenes (group A Streptococcus [GAS]), a major human-specific pathogen, relies on efficient nutrient acquisition for successful infection within its host. The phosphotransferase system (PTS) couples the import of carbohydrates with their phosphorylation prior to metabolism and has been linked to GAS pathogenesis. In a screen of an insertional mutant library of all 14 annotated PTS permease (EIIC) genes in MGAS5005, the annotated β-glucoside PTS transporter (bglP) was found to be crucial for GAS growth and survival in human blood and was validated in another M1T1 GAS strain, 5448. In 5448, bglP was shown...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Braza, R. E., Silver, A. B., Sundar, G. S., Davis, S. E., Razi, A., Islam, E., Hart, M., Zhu, J., Le Breton, Y., McIver, K. S. Tags: Molecular Pathogenesis Source Type: research

Multiple Ehrlichia chaffeensis Genes Critical for Its Persistent Infection in a Vertebrate Host Are Identified by Random Mutagenesis Coupled with In Vivo Infection Assessment [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
We reported earlier that the Himar1 transposon-based random mutagenesis is a valuable tool in defining E. chaffeensis genes critical for its persistent growth in vivo in reservoir and incidental hosts. The method also aided in extending studies focused on vaccine development and immunity. Here, we describe the generation and mapping of 55 new mutations. To define the critical nature of the bacterial genes, infection experiments were carried out in the canine host with pools of mutant organisms. Infection evaluation in the physiologically relevant host by molecular assays and by xenodiagnoses allowed the identification of m...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Wang, Y., Nair, A. D. S., Alhassan, A., Jaworski, D. C., Liu, H., Trinkl, K., Hove, P., Ganta, C. K., Burkhardt, N., Munderloh, U. G., Ganta, R. R. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Suppression of Chlamydial Pathogenicity by Nonspecific CD8+ T Lymphocytes [Molecular Pathogenesis]
Chlamydia trachomatis, a leading infectious cause of tubal infertility, induces upper genital tract pathology, such as hydrosalpinx, which can be modeled with Chlamydia muridarum infection in mice. Following C. muridarum inoculation, wild-type mice develop robust hydrosalpinx, but OT1 mice fail to do so because their T cell receptors are engineered to recognize a single ovalbumin epitope (OVA457-462). These observations have demonstrated a critical role of Chlamydia-specific T cells in chlamydial pathogenicity. In the current study, we have also found that OT1 mice can actively inhibit chlamydial pathogenicity. First, depl...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Xie, L., He, C., Chen, J., Tang, L., Zhou, Z., Zhong, G. Tags: Molecular Pathogenesis Source Type: research

Vaccination with Secreted Aspartyl Proteinase 2 Protein from Candida parapsilosis Can Enhance Survival of Mice during C. tropicalis-Mediated Systemic Candidiasis [Microbial Immunity and Vaccines]
This study investigated the protective efficacy of secreted aspartyl proteinase 2 (Sap2) in systemic C. tropicalis infection. Vaccination with recombinant Sap2 (rSap2) protein from C. parapsilosis enhanced survival of mice compared to rSap2 vaccinations from C. albicans (P = 0.02), C. tropicalis (P = 0.06), and sham immunization (P = 0.04). Compared to sham-immunized mice, the fungal CFU number was significantly reduced in organs of Sap2-parapsilosis-immunized mice. Histopathologically, increased neutrophilic recruitment was observed in Sap2-parapsilosis- and Sap2-tropicalis-immunized mice. Among different rSap2 proteins, ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Shukla, M., Rohatgi, S. Tags: Microbial Immunity and Vaccines Source Type: research

The Salmonella LysR Family Regulator RipR Activates the SPI-13-Encoded Itaconate Degradation Cluster [Molecular Pathogenesis]
Itaconate is a dicarboxylic acid that inhibits the isocitrate lyase enzyme of the bacterial glyoxylate shunt. Activated macrophages have been shown to produce itaconate, suggesting that these immune cells may employ this metabolite as a weapon against invading bacteria. Here, we demonstrate that in vitro, itaconate can exhibit bactericidal effects under acidic conditions similar to the pH of a macrophage phagosome. In parallel, successful pathogens, including Salmonella, have acquired a genetic operon encoding itaconate degradation proteins, which are induced heavily in macrophages. We characterized the regulation of this ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Hersch, S. J., Navarre, W. W. Tags: Molecular Pathogenesis Source Type: research

Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies [Molecular Pathogenesis]
Typhoid toxin is a virulence factor of Salmonella enterica serovar Typhi, the causative agent of typhoid fever, and is thought to be responsible for the symptoms of severe disease. This toxin has a unique A2B5 architecture with two active subunits, the ADP ribosyl transferase PltA and the DNase CdtB, linked to a pentameric B subunit, which is alternatively made of PltB or PltC. Here, we describe the generation and characterization of typhoid toxin-neutralizing human monoclonal antibodies by immunizing genetically engineered mice that have a full set of human immunoglobulin variable region genes. We identified several monoc...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Jiao, X., Smith, S., Stack, G., Liang, Q., Bradley, A., Kellam, P., Galan, J. E. Tags: Molecular Pathogenesis Source Type: research

Genome-Wide Mutagenesis Identifies Factors Involved in Enterococcus faecalis Vaginal Adherence and Persistence [Molecular Pathogenesis]
Enterococcus faecalis is a Gram-positive commensal bacterium native to the gastrointestinal tract and an opportunistic pathogen of increasing clinical concern. E. faecalis also colonizes the female reproductive tract, and reports suggest vaginal colonization increases following antibiotic treatment or in patients with aerobic vaginitis. Currently, little is known about specific factors that promote E. faecalis vaginal colonization and subsequent infection. We modified an established mouse vaginal colonization model to explore E. faecalis vaginal carriage and demonstrate that both vancomycin-resistant and -sensitive strains...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Alhajjar, N., Chatterjee, A., Spencer, B. L., Burcham, L. R., Willett, J. L. E., Dunny, G. M., Duerkop, B. A., Doran, K. S. Tags: Molecular Pathogenesis Source Type: research

Brucella abortus and Pregnancy in Mice: Impact of Chronic Infection on Fertility and the Role of Regulatory T Cells in Tissue Colonization [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate that Brucella abortus, a notorious reproductive pathogen, has the ability to infect the nonpregnant uterus, sustain infection, and induce inflammatory changes during both acute and chronic stages of infection. In addition, we demonstrated that chronically infected mice had a significa...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Adetunji, S. A., Faustman, D. L., Adams, L. G., Garcia-Gonzalez, D. G., Hensel, M. E., Khalaf, O. H., Arenas-Gamboa, A. M. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Diffusible Signal Factors Act through AraC-Type Transcriptional Regulators as Chemical Cues To Repress Virulence of Enteric Pathogens [Molecular Pathogenesis]
Successful colonization by enteric pathogens is contingent upon effective interactions with the host and the resident microbiota. These pathogens thus respond to and integrate myriad signals to control virulence. Long-chain fatty acids repress the virulence of the important enteric pathogens Salmonella enterica and Vibrio cholerae by repressing AraC-type transcriptional regulators in pathogenicity islands. While several fatty acids are known to be repressive, we show here that cis-2-unsaturated fatty acids, a rare chemical class used as diffusible signal factors (DSFs), are highly potent inhibitors of virulence functions. ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Bosire, E. M., Eade, C. R., Schiltz, C. J., Reid, A. J., Troutman, J., Chappie, J. S., Altier, C. Tags: Molecular Pathogenesis Source Type: research

Antibodies and Protection in Systemic Salmonella Infections: Do We Still Have More Questions than Answers? [Minireviews]
Salmonella causes grave systemic infections in humans and other animals and provides a paradigm for other diseases in which the bacteria have both intracellular and extracellular lifestyles. New generations of vaccines rely on the essential contribution of the antibody responses for their protection. The quality, antigen specificity, and functions associated with antibody responses to this pathogen have been elusive for a long time. Recent approaches that combine studies in humans and genetically manipulated experimental models and that exploit awareness of the location and within-host life cycle of the pathogen are sheddi...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Mastroeni, P., Rossi, O. Tags: Minireviews Source Type: research

Intratracheal Inoculation with Brucella melitensis in the Pregnant Guinea Pig Is an Improved Model for Reproductive Pathogenesis and Vaccine Studies [Microbial Immunity and Vaccines]
Reproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with Brucella melitensis is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model. Recently, it was demonstrated that intratracheal (IT) inoculation of nonpregnant guinea pigs would replicate features of clinical disease in humans. To determine if IT inoculation would induce reproductive disease, guinea pigs were infected at mid-gestation and...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Hensel, M. E., Chaki, S. P., Stranahan, L., Gregory, A. E., van Schaik, E. J., Garcia-Gonzalez, D. G., Khalaf, O., Samuel, J. E., Arenas-Gamboa, A. M. Tags: Microbial Immunity and Vaccines Source Type: research

Niche- and Gender-Dependent Immune Reactions in Relation to the Microbiota Profile in Pediatric Patients with Otitis Media with Effusion [Host-Associated Microbial Communities]
Otitis media with effusion (OME) is a common inflammatory disease that primarily affects children. OME is defined as a chronic low-grade inflammation of the middle ear (ME), without any signs of infection and with effusion persisting in the ME for more than 3 months. The precise pathogenesis is, however, not fully understood. Here, we comprehensively characterized and compared the host immune responses (inflammatory cells and mediators) and the overall microbial community composition (microbiota) present in matched middle ear effusion (MEE) samples, external ear canal (EEC) lavages, and nasopharynx (NPH) samples from child...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Enoksson, F., Ruiz Rodriguez, A., Peno, C., Balcazar Lopez, C., Tjernström, F., Bogaert, D., Hakansson, A. P., Bergenfelz, C. Tags: Host-Associated Microbial Communities Source Type: research

A Role of Epithelial Cells and Virulence Factors in Biofilm Formation by Streptococcus pyogenes In Vitro [Host-Associated Microbial Communities]
In this study, biofilm formation was measured on respiratory epithelial cells and keratinocytes by determining biomass and antibiotic resistance, and biofilm morphology was visualized using scanning electron microscopy. All GAS isolates tested formed biofilms that had similar, albeit not identical, biomass and antibiotic resistance for both cell types. Interestingly, functionally mature biofilms formed more rapidly on keratinocytes but were structurally denser and coated with more ECM on respiratory epithelial cells. The ECM was crucial for biofilm integrity, as protein- and DNA-degrading enzymes induced bacterial release ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Alamiri, F., Chao, Y., Baumgarten, M., Riesbeck, K., Hakansson, A. P. Tags: Host-Associated Microbial Communities Source Type: research

Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation [Molecular Pathogenesis]
This study tested the potential role of Rab small GTPase 5a (Rab5a) in the process. We tested mRNA and protein expression of proinflammatory cytokines (interleukin-1β [IL-1β] and IL-6) in THP-1 macrophages by quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs), respectively. In the primary colonic epithelial cells, Cdt treatment induced a CdtB-Rab5a-cellugyrin association. Rab5a silencing, by target small hairpin RNAs (shRNAs), largely inhibited CdtB-induced cytotoxicity and apoptosis in colon epithelial cells. CRISPR/Cas9-mediated Rab5a knockout also attenuated CdtB-induced colon epithelial c...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Chen, M.-x., Chen, Y., Fu, R., Mao, G.-q., Liu, S.-y., Shen, T.-b. Tags: Molecular Pathogenesis Source Type: research

Microscopic and Submicroscopic Asymptomatic Plasmodium falciparum Infections in Ghanaian Children and Protection against Febrile Malaria [Fungal and Parasitic Infections]
This study assessed the association between baseline microscopic and submicroscopic asymptomatic P. falciparum infections and antimalarial antibody levels and whether these parasitemia modify protective associations between antibody levels and malaria in Ghanaian children. Healthy children (N = 973, aged 0.5 to 12 years) were recruited into a 50-week longitudinal malaria cohort study from January 2016 to January 2017. Baseline asymptomatic parasitemia were determined by microscopy (microscopic parasitemia) and PCR (submicroscopic parasitemia), and antibody levels against crude schizont antigens were measured by enzyme-limi...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Adu, B., Issahaque, Q.-a., Sarkodie-Addo, T., Kumordjie, S., Kyei-Baafour, E., Sinclear, C. K., Eyia-Ampah, S., Owusu-Yeboa, E., Theisen, M., Dodoo, D. Tags: Fungal and Parasitic Infections Source Type: research

Immunization against Anaplasma phagocytophilum Adhesin Binding Domains Confers Protection against Infection in the Mouse Model [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In this study, C57BL/6 mice were immunized with a cocktail of keyhole limpet hemocyanin-conjugated peptides corresponding to the AipA, Asp14, and OmpA binding domains in alum followed by challenge with A. phagocytophilum. The bacterial peripheral blood burden was pronouncedly reduced in immunized mice compared to controls. Examination of pre- and postchallenge sera from these mice revealed that immunization elicited antibodies against AipA and Asp14 peptides but not OmpA peptide. Nonetheless, pooled sera from pre- and postchallenge groups, but not from control groups, inhibited A. phagocytophilum infection of HL-60 cells. ...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Naimi, W. A., Gumpf, J. J., Green, R. S., Izac, J. R., Zellner, M. P., Conrad, D. H., Marconi, R. T., Martin, R. K., Carlyon, J. A. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Tags: Masthead Source Type: research

Endocervical miRNA Expression Profiles in Women Positive for Chlamydia trachomatis with Clinical Signs and/or Symptoms Are Distinct from Those in Women Positive for Chlamydia trachomatis without Signs and Symptoms [Host Response and Inflammation]
Chlamydia trachomatis is the leading cause of sexually transmitted infections that may progress to pelvic inflammatory disease and infertility. No effective vaccine exists for Chlamydia, nor are there biomarkers available that readily predict disease progression. In this cross-sectional pilot study, we recruited symptomatic and asymptomatic women with C. trachomatis (CT) infection and asymptomatic, uninfected control women from an urban sexually transmitted disease clinic to determine if there were differences in microRNA (miRNA) expression. Infected women with signs and/or symptoms (CTSS) have distinct miRNA profiles comp...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Batteiger, T. A., Spencer, N., Washam, C. L., Byrum, S., Eledge, M., Batteiger, B. E., Rank, R. G., Yeruva, L. Tags: Host Response and Inflammation Source Type: research

The Novel Streptococcal Transcriptional Regulator XtgS Negatively Regulates Bacterial Virulence and Directly Represses PseP Transcription [Bacterial Infections]
In this study, we identified a novel XRE-family transcriptional regulator encoded on the GBS genome, designated XtgS. Our data demonstrate that XtgS inactivation significantly increases bacterial survival in host blood and animal challenge test, suggesting that it is a negative regulator of GBS pathogenicity. Further transcriptomic analysis and quantitative reverse transcription-PCR (qRT-PCR) mainly indicated that XtgS significantly repressed transcription of its upstream gene pseP. Based on electrophoretic mobility shift and lacZ fusion assays, we found that an XtgS homodimer directly binds a palindromic sequence in the p...
Source: Infection and Immunity - September 17, 2020 Category: Infectious Diseases Authors: Liu, G., Gao, T., Zhong, X., Ma, J., Zhang, Y., Zhang, S., Wu, Z., Pan, Z., Zhu, Y., Yao, H., Liu, Y., Lu, C. Tags: Bacterial Infections Source Type: research

Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis? [Minireviews]
A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. As there have been many criticisms of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human ...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Alverdy, J. C., Keskey, R., Thewissen, R. Tags: Minireviews Source Type: research

Neural Immune Communication in the Control of Host-Bacterial Pathogen Interactions in the Gastrointestinal Tract [Minireviews]
The orchestration of host immune responses to enteric bacterial pathogens is a complex process involving the integration of numerous signals, including from the nervous system. Despite the recent progress in understanding the contribution of neuroimmune interactions in the regulation of inflammation, the mechanisms and effects of this communication during enteric bacterial infection are only beginning to be characterized. As part of this neuroimmune communication, neurons specialized to detect painful or otherwise noxious stimuli can respond to bacterial pathogens. Highlighting the complexity of these systems, the immunolo...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Ramirez, V., Swain, S., Murray, K., Reardon, C. Tags: Minireviews Source Type: research

Distinct Morphological Fates of Uropathogenic Escherichia coli Intracellular Bacterial Communities: Dependency on Urine Composition and pH [Bacterial Infections]
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections. These bacteria undertake a multistage infection cycle involving invasion of and proliferation within urinary tract epithelial cells, leading to the rupture of the host cell and dispersal of the bacteria, some of which have a highly filamentous morphology. Here, we established a microfluidics-based model of UPEC infection of immortalized human bladder epithelial cells that recapitulates the main stages of bacterial morphological changes during the acute infection cycle in vivo and allows the development and fate of individual cells to be...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Iosifidis, G., Duggin, I. G. Tags: Bacterial Infections Source Type: research

Article of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Tags: Spotlight Source Type: research

Nontypeable Haemophilus influenzae Type IV Pilus Mediates Augmented Adherence to Rhinovirus-Infected Human Airway Epithelial Cells [Bacterial Infections]
Human rhinovirus (hRV) is frequently detected in the upper respiratory tract, and symptomatic infection is associated with an increased nasopharyngeal bacterial load, with subsequent development of secondary bacterial diseases. Nontypeable Haemophilus influenzae (NTHI) is a commensal bacterial species of the human nasopharynx; however, in the context of prior or concurrent upper respiratory tract viral infection, this bacterium commonly causes multiple diseases throughout the upper and lower respiratory tracts. The present study was conducted to determine the mechanism(s) by which hRV infection promotes the development of ...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Toone, S. L., Ratkiewicz, M., Novotny, L. A., Phong, B. L., Bakaletz, L. O. Tags: Bacterial Infections Source Type: research

Scnn1b-Transgenic BALB/c Mice as a Model of Pseudomonas aeruginosa Infections of the Cystic Fibrosis Lung [Bacterial Infections]
The opportunistic pathogen Pseudomonas aeruginosa is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections. P. aeruginosa lung infections are difficult to treat because P. aeruginosa adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of P. aeruginosa, modeling P. aeruginosa infections in CF has been challenging. Here, we characterize Scnn1b-transgenic (Tg) BALB/c mice as P. aeruginosa lung infection models. Scnn1b-Tg mice overexpress the epithelial Na+ channel (...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Brao, K. J., Wille, B. P., Lieberman, J., Ernst, R. K., Shirtliff, M. E., Harro, J. M. Tags: Bacterial Infections Source Type: research

Differential Interactions of Serum and Bronchoalveolar Lavage Fluid Complement Proteins with Conidia of Airborne Fungal Pathogen Aspergillus fumigatus [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In this study, we aimed at deciphering the role of the complement system, the major humoral immune component, against A. fumigatus. Mass spectrometry analysis of the proteins extracted from A. fumigatus conidial (asexual spores and infective propagules) surfaces opsonized with human serum indicated that C3 is the major complement protein involved. Flow cytometry and immunolabeling assays further confirmed C3b (activated C3) deposition on the conidial surfaces. Assays using cell wall components of conidia indicated that the hydrophobin RodAp, β-(1,3)-glucan (BG) and galactomannan (GM) could efficiently activate C3. Usi...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Wong, S. S. W., Daniel, I., Gangneux, J.-P., Jayapal, J. M., Guegan, H., Delliere, S., Lalitha, P., Shende, R., Madan, T., Bayry, J., Guijarro, J. I., Kuppamuthu, D., Aimanianda, V. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Activation of the NLRP3 Inflammasome by Particles from the Echinococcus granulosus Laminated Layer [Host Response and Inflammation]
The interaction of dendritic cells and macrophages with a variety of rigid noncellular particles triggers activation of the NLRP3 inflammasome and consequent secretion of interleukin 1β (IL-1β). Noncellular particles can also be generated in the context of helminth infection, since these large pathogens often shed their outermost structures during growth and/or molting. One such structure is the massive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stages of cestodes of the genus Echinococcus. We show that particles from the Echinococcus granulosus LL (pLL) trigger NLRP3- and caspas...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Casaravilla, C., Pittini, A., Rückerl, D., Allen, J. E., Diaz, A. Tags: Host Response and Inflammation Source Type: research

Aggregative Adherence Fimbriae II of Enteroaggregative Escherichia coli Are Required for Adherence and Barrier Disruption during Infection of Human Colonoids [Bacterial Infections]
In this study, we investigated the role of the aggregative adherence fimbriae II (AAF/II) in EAEC adherence and pathogenesis using human colonoids and duodenal enteroids. We found that a null mutant in aafA, the major subunit of AAF/II, adhered significantly less than wild-type (WT) EAEC strain 042, and adherence was restored in a complemented strain. Immunofluorescence confocal microscopy of differentiated colonoids, which produce an intact mucus layer comprised of the secreted mucin MUC2, revealed bacteria at the epithelial surface and within the MUC2 layer. The WT strain adhered to the epithelial surface, whereas the aa...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Gonyar, L. A., Smith, R. M., Giron, J. A., Zachos, N. C., Ruiz-Perez, F., Nataro, J. P. Tags: Bacterial Infections Source Type: research

A Small Membrane Stabilizing Protein Critical to the Pathogenicity of Staphylococcus aureus [Molecular Pathogenesis]
Staphylococcus aureus is a major human pathogen, and the emergence of antibiotic-resistant strains is making all types of S. aureus infections more challenging to treat. With a pressing need to develop alternative control strategies to use alongside or in place of conventional antibiotics, one approach is the targeting of established virulence factors. However, attempts at this have had little success to date, suggesting that we need to better understand how this pathogen causes disease if effective targets are to be identified. To address this, using a functional genomics approach, we have identified a small membrane-boun...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Duggan, S., Laabei, M., Alnahari, A. A., OBrien, E. C., Lacey, K. A., Bacon, L., Heesom, K., Fu, C.-L., Otto, M., Skaar, E., McLoughlin, R. M., Massey, R. C. Tags: Molecular Pathogenesis Source Type: research

The Ethanolamine-Sensing Transcription Factor EutR Promotes Virulence and Transmission during Citrobacter rodentium Intestinal Infection [Molecular Pathogenesis]
Enteric pathogens exploit chemical and nutrient signaling to gauge their location within a host and control expression of traits important for infection. Ethanolamine-containing molecules are essential in host physiology and play important roles in intestinal processes. The transcription factor EutR is conserved in the Enterobacteriaceae and is required for ethanolamine sensing and metabolism. In enterohemorrhagic Escherichia coli (EHEC) O157:H7, EutR responds to ethanolamine to activate expression of traits required for host colonization and disease; however, the importance of EutR to EHEC intestinal infection has not bee...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Rowley, C. A., Sauder, A. B., Kendall, M. M. Tags: Molecular Pathogenesis Source Type: research

Human Fallopian Tube Epithelial Cell Culture Model To Study Host Responses to Chlamydia trachomatis Infection [Host Response and Inflammation]
Chlamydia trachomatis infection of the human fallopian tubes can lead to damaging inflammation and scarring, ultimately resulting in infertility. To study the human cellular responses to chlamydial infection, researchers have frequently used transformed cell lines that can have limited translational relevance. We developed a primary human fallopian tube epithelial cell model based on a method previously established for culture of primary human bronchial epithelial cells. After protease digestion and physical dissociation of excised fallopian tubes, epithelial cell precursors were expanded in growth factor-containing medium...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: McQueen, B. E., Kiatthanapaiboon, A., Fulcher, M. L., Lam, M., Patton, K., Powell, E., Kollipara, A., Madden, V., Suchland, R. J., Wyrick, P., OConnell, C. M., Reidel, B., Kesimer, M., Randell, S. H., Darville, T., Nagarajan, U. M. Tags: Host Response and Inflammation Source Type: research

A 20-Mer Peptide Derived from the Lectin Domain of SP-A2 Decreases Tumor Necrosis Factor Alpha Production during Mycoplasma pneumoniae Infection [Host Response and Inflammation]
Human surfactant protein-A2 (hSP-A2) is a component of pulmonary surfactant that plays an important role in the lung’s immune system by interacting with viruses, bacteria, and fungi to facilitate pathogen clearance and by downregulating inflammatory responses after an allergic challenge. Genetic variation in SP-A2 at position Gln223Lys is present in up to ~30% of the population and has been associated with several lung diseases, such as asthma, pulmonary fibrosis, and lung cancer (M. M. Pettigrew, J. F. Gent, Y. Zhu, E. W. Triche, et al., BMC Med Genet 8:15, 2007, https://bmcmedgenet.biomedcentral.com/articles/10.118...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Younis, U. S., Chu, H. W., Kraft, M., Ledford, J. G. Tags: Host Response and Inflammation Source Type: research

The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection [Host Response and Inflammation]
C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-B is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-B could profoundly influence host defense against fungal pathogens. However, little is known about the mechanisms that negatively regulate CLR-induced NF-B, and molecules which act on the CLR family broadly and which directly regulate acute CLR-signaling cascades remain unidentified. Here, we identify the ubiquitin-editing enzyme A20 as a negative regulator of acute NF-B activation downstream of multiple CLR pathways. Absence of A20 s...
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Authors: Liang, J., Zhang, J. J., Huang, H.-I., Kanayama, M., Youssef, N., Jin, Y. J., Reyes, E. Y., Abram, C. L., Yang, S., Lowell, C. A., Wang, D., Shao, L., Shinohara, M. L., Zhang, J. Y., Hammer, G. E. Tags: Host Response and Inflammation Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - August 18, 2020 Category: Infectious Diseases Tags: Masthead Source Type: research

Morphological and Motility Features of the Stable Bleb-Driven Monopodial Form of Entamoeba and Its Importance in Encystation [Fungal and Parasitic Infections]
Entamoeba histolytica and its reptilian counterpart and encystation model Entamoeba invadens formed a polarized monopodial morphology when treated with pentoxifylline. This morphology was propelled by retrograde flow of the cell surface resulting from a cyclic sol-gel conversion of cytoplasm and a stable bleb at the leading edge. Pentoxifylline treatment switched the unpolarized, adherent trophozoites to the nonadherent, stable bleb-driven form and altered the motility pattern from slow and random to fast, directionally persistent, and highly chemotactic. Interestingly, exogenously added adenosine produced multiple protrus...
Source: Infection and Immunity - July 20, 2020 Category: Infectious Diseases Authors: Krishnan, D., Ghosh, S. K. Tags: Fungal and Parasitic Infections Source Type: research

Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Xenophagy targets intracellular pathogens for destruction by the host autophagy pathway. Ubiquitin chains are conjugated to xenophagic targets and recruit multiple autophagy adaptors. The intracellular pathogen Legionella pneumophila resides in a vacuole that is ubiquitinated; however, this pathogen avoids xenophagic detection. Here, the mechanisms by which L. pneumophila can prevent the host xenophagy pathway from targeting the vacuole in which it resides were examined. Ubiquitin-labeled vacuoles containing L. pneumophila failed to recruit autophagy adaptors by a process that was independent of RavZ function. Coinfection ...
Source: Infection and Immunity - July 20, 2020 Category: Infectious Diseases Authors: Omotade, T. O., Roy, C. R. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research