Atypical Enteropathogenic Escherichia coli: from Kittens to Humans and Beyond! [Commentary]
Atypical enteropathogenic Escherichia coli (aEPEC) are associated with diarrhea worldwide, yet genome-wide investigations to probe their virulome are lacking. In this issue of Infection and Immunity, V. E. Watson, T. H. Hazen, D. A. Rasko, M. E. Jacob, et al. (IAI 89:e00619-20, 2020, https://doi.org/10.1128/IAI.00619-20) sequenced aEPEC isolates from diarrheic and asymptomatic kittens. Using phylogenomics, they demonstrated that these isolates were genetically indistinguishable from human isolates, suggesting that kittens may serve as a reservoir and, perhaps, a much-needed model to interrogate aEPEC virulence. The diarrhe...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Bhatt, S. Tags: Commentary Source Type: research

Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis [Host Response and Inflammation]
In this study, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2–/–) and wild-type (WT) mice. We revealed that Fpr2–/– mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we fo...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Ni, C., Gao, S., Zheng, Y., Liu, P., Zhai, Y., Huang, W., Jiang, H., Lv, Q., Kong, D., Jiang, Y. Tags: Host Response and Inflammation Source Type: research

Comparative Genomics of Atypical Enteropathogenic Escherichia coli from Kittens and Children Identifies Bacterial Factors Associated with Virulence in Kittens [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Typical enteropathogenic Escherichia coli (tEPEC) is a leading cause of diarrhea and associated death in children worldwide. Atypical EPEC (aEPEC) lacks the plasmid encoding bundle-forming pili and is considered less virulent, but the molecular mechanism of virulence is poorly understood. We recently identified kittens as a host for aEPEC where intestinal epithelial colonization was associated with diarrheal disease and death. The purposes of this study were to (i) determine the genomic similarity between kitten aEPEC and human aEPEC isolates and (ii) identify genotypic or phenotypic traits associated with virulence in kit...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Watson, V. E., Hazen, T. H., Rasko, D. A., Jacob, M. E., Elfenbein, J. R., Stauffer, S. H., Gookin, J. L. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice [Microbial Immunity and Vaccines]
In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased th...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Wolf, M. A., Boehm, D. T., DeJong, M. A., Wong, T. Y., Sen-Kilic, E., Hall, J. M., Blackwood, C. B., Weaver, K. L., Kelly, C. O., Kisamore, C. A., Bitzer, G. J., Bevere, J. R., Barbier, M., Damron, F. H. Tags: Microbial Immunity and Vaccines Source Type: research

Salmonella enterica Serovars Dublin and Enteritidis Comparative Proteomics Reveals Differential Expression of Proteins Involved in Stress Resistance, Virulence, and Anaerobic Metabolism [Molecular Pathogenesis]
The Enteritidis and Dublin serovars of Salmonella enterica are phylogenetically closely related yet differ significantly in host range and virulence. S. Enteritidis is a broad-host-range serovar that commonly causes self-limited gastroenteritis in humans, whereas S. Dublin is a cattle-adapted serovar that can infect humans, often resulting in invasive extraintestinal disease. The mechanism underlying the higher invasiveness of S. Dublin remains undetermined. In this work, we quantitatively compared the proteomes of clinical isolates of each serovar grown under gut-mimicking conditions. Compared to S. Enteritidis, the S. Du...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Martinez-Sanguine, A. Y., DAlessandro, B., Langleib, M., Traglia, G. M., Monaco, A., Duran, R., Chabalgoity, J. A., Betancor, L., Yim, L. Tags: Molecular Pathogenesis Source Type: research

Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague [Host Response and Inflammation]
Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of Y. pestis, inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection. We previously showed that Y. pestis lacking the 102-kb chromosomal pigmentation locus (pgm) is unable to cause inflammatory damage in the lungs, whereas the wild-type (WT) strain induces the toxic MyD88 pulmonary inflammatory respon...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Olson, R. M., Dhariwala, M. O., Mitchell, W. J., Skyberg, J. A., Anderson, D. M. Tags: Host Response and Inflammation Source Type: research

Acetylation of PhoP K88 Is Involved in Regulating Salmonella Virulence [Molecular Pathogenesis]
The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of S. Typhimurium. Here, we demonstrate that a conserved lysine residue, K88, is crucial for the function of PhoP and its acetylation-downregulated PhoP activities. K88 could be specifically acetylated by acetyl phosphate (AcP), and the acetylation level of K88 decreased signific...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Li, J., Liu, S., Su, Y., Ren, J., Sang, Y., Ni, J., Lu, J., Yao, Y.-F. Tags: Molecular Pathogenesis Source Type: research

Systematic Evaluation of Mycobacterium tuberculosis Proteins for Antigenic Properties Identifies Rv1485 and Rv1705c as Potential Protective Subunit Vaccine Candidates [Microbial Immunity and Vaccines]
The lack of efficacious vaccines against Mycobacterium tuberculosis (MTB) infection is a limiting factor in the prevention and control of tuberculosis (TB), the leading cause of death from an infectious agent. Improvement or replacement of the BCG vaccine with one that reliably protects all age groups is urgent. Concerns exist that antigens currently being evaluated are too homogeneous. To identify new protective antigens, we screened 1,781 proteins from a high-throughput proteome-wide protein purification study for antigenic activity. Forty-nine antigens (34 previously unreported) induced antigen-specific gamma interferon...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Wang, Y., Li, Z., Wu, S., Fleming, J., Li, C., Zhu, G., Chen, B., Ren, B., Wang, X., Du, B., Li, P., Hu, P., Yang, J., Liu, Y., Zhou, C., Zhang, X.-E., Bi, L., Zhang, H., Yang, J., Zhang, Z. Tags: Microbial Immunity and Vaccines Source Type: research

Slipped-Strand Mispairing in the Gene Encoding Sialidase NanH3 in Gardnerella spp. [Host-Associated Microbial Communities]
Cell wall proteins with sialidase activity are involved in carbohydrate assimilation, adhesion to mucosal surfaces, and biofilm formation. Gardnerella spp. inhabit the human vaginal microbiome and encode up to three sialidase enzymes, two of which are suspected to be cell wall associated. Here, we demonstrate that the gene encoding extracellular sialidase NanH3 is found almost exclusively in Gardnerella piotii and the closely related species Gardnerella genome sp. 3, and its presence correlates with a sialidase-positive phenotype in a collection of 112 Gardnerella isolates. The nanH3 gene sequence includes a homopolymeric ...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Kurukulasuriya, S. P., Patterson, M. H., Hill, J. E. Tags: Host-Associated Microbial Communities Source Type: research

Innate IFN-{gamma} Is Essential for Systemic Chlamydia muridarum Control in Mice, While CD4 T Cell-Dependent IFN-{gamma} Production Is Highly Redundant in the Female Reproductive Tract [Microbial Immunity and Vaccines]
In this study, we dissected the requirements of IFN- produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal infection, IFN--deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFN- and CD4 T cells in host defense against Chlamydia. In Rag1-deficient mice, IFN- produced by innate lymphocytes (ILCs) accounted for early bacterial control and prolonged survival in the absence of adaptive immunity. Although type ...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Mercado, M. A. B., Du, W., Malaviarachchi, P. A., Gann, J. I., Li, L.-X. Tags: Microbial Immunity and Vaccines Source Type: research

Establishment and Validation of Pathogenic CS17+ and CS19+ Enterotoxigenic Escherichia coli Challenge Models in the New World Primate Aotus nancymaae [Microbial Immunity and Vaccines]
Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrheal illness in the military, travelers, and children living in low- to middle-income countries. Increased antibiotic resistance, the absence of a licensed vaccine, and the lack of broadly practical therapeutics perpetuate the significant health and financial burden resulting from ETEC infection. A critical step in the evaluation of vaccines and therapeutics is preclinical screening in a relevant animal disease model that closely replicates human disease. We previously developed a diarrheal model of class 5a colonization factor (CF) CFA/I-expressing ETEC in ...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Hall, E. R., O'Dowd, A., Rollenhagen, J. E., Espinoza, N., Nunez, G., Savarino, S. J. Tags: Microbial Immunity and Vaccines Source Type: research

STAT3 Promotes Schistosome-Induced Liver Injury by Inflammation, Oxidative Stress, Proliferation, and Apoptosis Signal Pathway [Fungal and Parasitic Infections]
In this study, C57BL/6 wild-type mice and Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum. Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Zhao, J., Liu, X., Chen, Y., Zhang, L.-S., Zhang, Y.-R., Ji, D.-R., Liu, S.-M., Jia, M.-Z., Zhu, Y.-H., Qi, Y.-F., Lu, F.-M., Yu, Y.-R. Tags: Fungal and Parasitic Infections Source Type: research

Identification of Candida glabrata Transcriptional Regulators That Govern Stress Resistance and Virulence [Fungal and Parasitic Infections]
The mechanisms by which Candida glabrata resists host defense peptides and caspofungin are incompletely understood. To identify transcriptional regulators that enable C. glabrata to withstand these classes of stressors, a library of 215 C. glabrata transcriptional regulatory deletion mutants was screened for susceptibility to both protamine and caspofungin. We identified eight mutants that had increased susceptibility to both host defense peptides and caspofungin. Of these mutants, six were deleted for genes that were predicted to specify proteins involved in histone modification. These genes were ADA2, GCN5, SPT8, HOS2, R...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: Filler, E. E., Liu, Y., Solis, N. V., Wang, L., Diaz, L. F., Edwards, J. E., Filler, S. G., Yeaman, M. R. Tags: Fungal and Parasitic Infections Source Type: research

Genetic Variation in Toll-Like Receptor 5 and Colonization with Flagellated Bacterial Vaginosis-Associated Bacteria [Host-Associated Microbial Communities]
Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women with BV, including Mobiluncus spp. and BV-associated bacterium-1 (BVAB1), an uncultivated, putatively flagellated species. The host response to flagellin mediated through Toll-like receptor 5 (TLR5) has not been explored in BV. Using independent discovery and validation cohorts, we examined the hypothesis that TLR5 deficiency—defined by a dominant negative stop codon polymorphism, rs5744168—is associated with an increased risk for BV and increas...
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Authors: dela Cruz, E. J., Fiedler, T. L., Liu, C., Munch, M. M., Kohler, C. M., Oot, A. R., Wallis, J. M., Wang, J., Frishman, A., Garcia, K., Wiser, A., Balkus, J. E., Srinivasan, S., Golob, J. L., Sycuro, L. K., Marrazzo, J. M., Hawn, T. R., Fredricks, D. N. Tags: Host-Associated Microbial Communities Source Type: research

Article of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Tags: Spotlight Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - February 16, 2021 Category: Infectious Diseases Tags: Masthead Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Tags: Spotlight Source Type: research

Bile Salts Differentially Enhance Resistance of Enterohemorrhagic Escherichia coli O157:H7 to Host Defense Peptides [Molecular Pathogenesis]
During passage through the human gastrointestinal tract, enterohemorrhagic Escherichia coli (EHEC) is exposed to membrane-damaging bile in the small intestine. We previously reported that EHEC treatment with a physiological bile salt mixture upregulates basRS, encoding a two-component system, and arnBCADTEF, encoding the aminoarabinose lipid A modification pathway (J. V. Kus, A. Gebremedhin, V. Dang, S. L. Tran, A. Serbanescu, and D. Barnett Foster, J Bacteriol 193: 4509–4515, 2011, https://doi.org/10.1128/JB.00200-11). The present study examined the effect of bile salt mix (BSM) treatment on EHEC resistance to three...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Gadishaw-Lue, C., Banaag, A., Birstonas, S., Francis, A.-S., Barnett Foster, D. Tags: Molecular Pathogenesis Source Type: research

Rui Appelberg (1960-2020) [Editorial]
(Source: Infection and Immunity)
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Tags: Editorial Source Type: research

Gastric Metabolomics Detects Helicobacter pylori Correlated Loss of Numerous Metabolites in Both the Corpus and Antrum [Bacterial Infections]
Helicobacter pylori is a chronic bacterial pathogen that thrives in several regions of the stomach, causing inflammation that can vary by site and result in distinct disease outcomes. Whether the regions differ in terms of host-derived metabolites is not known. We thus characterized the regional variation of the metabolomes of mouse gastric corpus and antrum organoids and tissue. The uninfected secreted organoid metabolites differed between the corpus and antrum in only seven metabolites as follows: lactic acid, malic acid, phosphoethanolamine, alanine, uridine, glycerol, and isoleucine. Several of the secreted chemicals w...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Keilberg, D., Steele, N., Fan, S., Yang, C., Zavros, Y., Ottemann, K. M. Tags: Bacterial Infections Source Type: research

Acid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Previous studies have shown that sphingosine kills a variety of pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. Sphingosine concentrations are decreased in airway epithelial cells of cystic fibrosis (CF) mice, and this defect has been linked to the infection susceptibility of these mice. Here, we tested whether the genetic overexpression of acid ceramidase rescues cystic fibrosis mice from pulmonary infections with P. aeruginosa. We demonstrate that the transgenic overexpression of acid ceramidase in CF mice corresponds to the overexpression of acid ceramidase in bronchial and tracheal epit...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Becker, K. A., Verhaegh, R., Verhasselt, H.-L., Keitsch, S., Soddemann, M., Wilker, B., Wilson, G. C., Buer, J., Ahmad, S. A., Edwards, M. J., Gulbins, E. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague [Molecular Pathogenesis]
Yersinia pestis is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with Y. pestis is nearly 100% lethal within 4 to 7 days without antibiotic intervention. Pneumonic plague progresses in two phases, beginning with extensive bacterial replication in the lung with minimal host responsiveness, followed by the abrupt onset of a lethal proinflammatory response. The precise mechanisms by which Y. pestis is able to colonize the lung and survive two very distinct disease phases remain largely unknown....
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Crane, S. D., Banerjee, S. K., Eichelberger, K. R., Kurten, R. C., Goldman, W. E., Pechous, R. D. Tags: Molecular Pathogenesis Source Type: research

A Chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro [Microbial Immunity and Vaccines]
This study provides support for a new multiantigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against P. vivax malaria using sister species P. cynomolgi. (Source: Infection and Immunity)
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Shen, F.-h., Ong, J. J. Y., Sun, Y.-f., Lei, Y., Chu, R.-l., Kassegne, K., Fu, H.-t., Jin, C., Han, E.-T., Russell, B., Han, J.-H., Cheng, Y. Tags: Microbial Immunity and Vaccines Source Type: research

(p)ppGpp-Dependent Regulation of the Nucleotide Hydrolase PpnN Confers Complement Resistance in Salmonella enterica Serovar Typhimurium [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The stringent response is an essential mechanism of metabolic reprogramming during environmental stress that is mediated by the nucleotide alarmones guanosine tetraphosphate and pentaphosphate [(p)ppGpp]. In addition to physiological adaptations, (p)ppGpp also regulates virulence programs in pathogenic bacteria, including Salmonella enterica serovar Typhimurium. S. Typhimurium is a common cause of acute gastroenteritis, but it may also spread to systemic tissues, resulting in severe clinical outcomes. During infection, S. Typhimurium encounters a broad repertoire of immune defenses that it must evade for successful host in...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Chau, N. Y. E., Perez-Morales, D., Elhenawy, W., Bustamante, V. H., Zhang, Y. E., Coombes, B. K. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Neutral Vaginal pH in Mice That Is Typical of Most Mammalian Species Should Not Deter Research Using Experimental Murine Models of Candida Vaginitis [Commentary]
For over three decades, investigators have used estrogen-dependent rodent animal models to study pathogenesis of vulvovaginal candidiasis (VVC) or test promising antifungal drugs. One disparity not well publicized is that rodents maintain near neutral vaginal pH, which is in contrast to the acidic vaginal pH in women. In this issue of Infection and Immunity, Miao and coworkers (J. Miao, H. M. E. Willems, and B. M. Peters, Infect Immun 89:e00550-20, 2021, https://doi.org/10.1128/IAI.00550-20) have addressed the topic with an elegant study that not only confirms the near neutral vaginal pH in mice, but also reveals a stable ...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Fidel, P. L. Tags: Commentary Source Type: research

The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway [Molecular Pathogenesis]
In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP modulator, PrtR, which was shown to repress pyocin production by inhibition of PrtN and activate the type III secretion system (T3SS) through PtrB. Compared to a wild-type strain or a prtN mutant, the prtR prtN double mutant exhibited a wrinkly colony and hyperbiofilm phenotype, as well as an increase in intrace...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Jiao, H., Li, F., Wang, T., Yam, J. K. H., Yang, L., Liang, H. Tags: Molecular Pathogenesis Source Type: research

The Role of luxS in Histophilus somni Virulence and Biofilm Formation [Molecular Pathogenesis]
S-Ribosylhomocysteinase (LuxS) is required for the synthesis of the autoinducer-2 (AI-2) quorum-sensing signaling molecule in many Gram-negative bacteria. The bovine (and ovine) opportunistic pathogen Histophilus somni contains luxS and forms a biofilm containing an exopolysaccharide (EPS) in the matrix. Since biofilm formation is regulated by quorum sensing in many bacteria, the roles of luxS in H. somni virulence and biofilm formation were investigated. Although culture supernatants from H. somni were ineffective at inducing bioluminescence in the Vibrio harveyi reporter strain BB170, H. somni luxS complemented the biosy...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Pan, Y., Siddaramappa, S., Sandal, I., Dickerman, A., Bandara, A. B., Inzana, T. J. Tags: Molecular Pathogenesis Source Type: research

Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils [Minireviews]
Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26 to 37°C), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes and signaling pathways. HSPs assist cells in multiple functions, including differentiation, adaptation, virulence, and persistence in the host cell. Due to cyclical epidemiological patterns, limi...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Prasanna, P., Upadhyay, A. Tags: Minireviews Source Type: research

Exogenous Reproductive Hormones nor Candida albicans Colonization Alter the Near Neutral Mouse Vaginal pH [Host Response and Inflammation]
While human vaginal pH in childbearing-age women is conclusively acidic, the mouse vaginal pH is reported as being near neutral. However, this information appears to be somewhat anecdotal with respect to vulvovaginal candidiasis, as such claims in the literature frequently lack citations of studies that specifically address this physiological factor. Given the disparate pH between mice and humans, the role of exogenous hormones and colonization by the fungal pathogen Candida albicans in shaping vaginal pH was assessed. Use of a convenient modified vaginal lavage technique with the pH indicator dye phenol red demonstrated t...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Miao, J., Willems, H. M. E., Peters, B. M. Tags: Host Response and Inflammation Source Type: research

Adoptive Transfer of Group 3-Like Innate Lymphoid Cells Restores Mouse Colon Resistance to Colonization of a Gamma Interferon-Susceptible Chlamydia muridarum Mutant [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The obligate intracellular bacterium Chlamydia muridarum can colonize the mouse colon for a long period, but a gamma interferon (IFN-)-susceptible mutant clone fails to do so. Nevertheless, the mutant’s colonization is rescued in mice deficient in interleukin-7 receptor (IL-7R) (lacking both lymphocytes and innate lymphoid cells [ILCs]) or IFN- but not in mice lacking recombination-activated gene 1 (Rag1–/– mice) (lacking adaptive immunity lymphocytes), indicating a critical role of ILC-derived IFN- in regulating chlamydial colonization. In the current study, we have used an adoptive transfer approach for...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: He, Y., Xu, H., Song, C., Koprivsek, J. J., Arulanandam, B., Yang, H., Tao, L., Zhong, G. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia [Microbial Immunity and Vaccines]
In this study, we investigated the mechanistic correlates of protection of a curdlan-adjuvanted P. aeruginosa whole-cell vaccine (WCV) delivered intranasally. The WCV significantly decreased bacterial loads in the respiratory tract after intranasal P. aeruginosa challenge and raised antigen-specific antibody titers. To study the role of B and T cells during vaccination, anti-CD4, -CD8, and -CD20 depletions were performed prior to WCV vaccination and boosting. The depletion of CD4+, CD8+, or CD20+ cells had no impact on the bacterial burden in mock-vaccinated animals. However, depletion of CD20+ B cells, but not CD8+ or CD4...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Sen-Kilic, E., Blackwood, C. B., Huckaby, A. B., Horspool, A. M., Weaver, K. L., Malkowski, A. C., Witt, W. T., Bevere, J. R., Damron, F. H., Barbier, M. Tags: Microbial Immunity and Vaccines Source Type: research

cAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
We report here that CT triggers the UPR after 4 h of toxin exposure. A functional toxin was required to induce the UPR, but, surprisingly, activation of the adenylate cyclase signaling pathway was not sufficient to trigger the process. Toxin-induced activation of the UPR coincided with increased toxin accumulation in the cytosol. Chemical activation of the heterotrimeric G protein or the UPR also enhanced the onset of CTA1 delivery to the cytosol, thus producing a toxin-sensitive phenotype. These results indicate there is a cAMP-independent response to CT that activates the UPR and thereby enhances the efficiency of intoxi...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Banerjee, T., Grabon, A., Taylor, M., Teter, K. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Eukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Chlamydia trachomatis, an obligate intracellular pathogen, undergoes a biphasic developmental cycle within a membrane-bound vacuole called the chlamydial inclusion. To facilitate interactions with the host cell, Chlamydia modifies the inclusion membrane with type III secreted proteins, called Incs. As with all chlamydial proteins, Incs are temporally expressed, modifying the chlamydial inclusion during the early and mid-developmental cycle. VAMP3 and VAMP4 are eukaryotic SNARE proteins that mediate membrane fusion and are recruited to the inclusion to facilitate inclusion expansion. Their recruitment requires de novo chlam...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Bui, D.-C., Jorgenson, L. M., Ouellette, S. P., Rucks, E. A. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Targeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-{kappa}B Signaling Pathway in Sepsis [Bacterial Infections]
Neuropilin-1 (Nrp-1) contributes to maintaining the stability of CD4+ CD25+ regulatory T cells (Tregs). We investigated the impact of Nrp-1 on the stability of CD4+ CD25+ Tregs, and the underlying signaling pathways, in a model of sepsis. Splenic CD4+ CD25+ Tregs were either treated with anti-Nrp-1, transfected to silence Nrp-1 and inhibitor of NF-B kinase subunit beta (IKKβ), or administered ammonium pyrrolidine dithiocarbamate (PDTC), followed by recombinant semaphorin 3A (rSema3A), in a simulation of sepsis. After the creation of a sepsis model in mice, anti-Nrp-1 was administered. The expression of the gene encodi...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Gao, Y.-l., Wang, C.-x., Wang, Z.-y., Li, W.-j., Liu, Y.-c., Shou, S.-t., Chai, Y.-f. Tags: Bacterial Infections Source Type: research

Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The majority of Gram-negative bacteria elicit a potent immune response via recognition of lipid A expressed on the outer bacterial membrane by the host immune receptor Toll-like receptor 4 (TLR4). However, some Gram-negative bacteria evade detection by TLR4 or alter the outcome of TLR4 signaling by modification of lipid A species. Although the role of lipid A modifications on host innate immunity has been examined in some detail, it is currently unclear how lipid A remodeling influences host adaptive immunity. One prototypic Gram-negative bacterium that modifies its lipid A structure is Porphyromonas gingivalis, an anaerob...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Papadopoulos, G., Berland, R., Sunkavalli, A., Coats, S. R., Darveau, R. P., Genco, C. A. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Cardiotropic Isolates of Listeria monocytogenes with Enhanced Vertical Transmission Dependent upon the Bacterial Surface Protein InlB [Bacterial Infections]
Listeria monocytogenes is a facultative Gram-positive intracellular bacterium that is capable of causing serious invasive infections in pregnant women, resulting in abortion, still-birth, and disseminated fetal infection. Previously, a clinical L. monocytogenes isolate, 07PF0776, was identified as having an enhanced ability to target cardiac tissue. This tissue tropism appeared to correlate with amino acid variations found within internalin B (InlB), a bacterial surface protein associated with host cell invasion. Given that the mammalian receptor bound by InlB, Met, is abundantly expressed by placental tissue, we assessed ...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Lamond, N. M., McMullen, P. D., Paramasvaran, D., Visvahabrathy, L., Eallonardo, S. J., Maheswhari, A., Freitag, N. E. Tags: Bacterial Infections Source Type: research

CXCR3-Dependent Immune Pathology in Mice following Infection with Toxoplasma gondii during Early Pregnancy [Host Response and Inflammation]
In this study, we investigated the role of CXCR3 in fetal wastage caused by T. gondii infection using CXCR3-deficient (CXCR3–/–) mice. CXCR3–/– and wild-type pregnant mice were inoculated intraperitoneally with T. gondii tachyzoites on day 3.5 of gestation (Gd3.5). Pregnancy rates decreased as the pregnancy progressed in both infected groups; however, infected CXCR3–/– mice showed a significant fetal loss at Gd13.5 compared with that at Gd7.5. All embryos of the infected groups showed necrosis, and embryo resorption was significantly increased in infected CXCR3–/– compared wi...
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Authors: Nishida, A., Ikeda, R., Furuoka, H., Nishikawa, Y. Tags: Host Response and Inflammation Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - January 19, 2021 Category: Infectious Diseases Tags: Masthead Source Type: research

Interleukin-8 Receptor 2 (IL-8R2)-Deficient Mice Are More Resistant to Pulmonary Coccidioidomycosis than Control Mice [Fungal and Parasitic Infections]
The pathology of human coccidioidomycosis is granulomatous inflammation with many neutrophils surrounding ruptured spherules, but the chemotactic pathways that draw neutrophils into the infected tissues are not known. We previously showed that formalin-killed spherules (FKS) stimulate mouse macrophages to secret macrophage inflammatory protein 2 (MIP-2), which suggested that CXC ELR+ chemokines might be involved in neutrophil recruitment in vivo. To test that hypothesis, we intranasally infected interleukin-8R2 (IL-8R2) (Cxcr2)-deficient mice on a BALB/c background with Coccidioides immitis RS. IL-8R2-deficient mice had fe...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Carlin, A. F., Viriyakosol, S., Okamoto, S., Walls, L., Fierer, J. Tags: Fungal and Parasitic Infections Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Tags: Spotlight Source Type: research

Burkholderia pseudomallei as an Enteric Pathogen: Identification of Virulence Factors Mediating Gastrointestinal Infection [Bacterial Infections]
Burkholderia pseudomallei is a Gram-negative bacterium and the causative agent of melioidosis. Despite advances in our understanding of the disease, B. pseudomallei poses a significant health risk, especially in regions of endemicity, where treatment requires prolonged antibiotic therapy. Even though the respiratory and percutaneous routes are well documented and considered the main ways to acquire the pathogen, the gastrointestinal tract is believed to be an underreported and underrecognized route of infection. In the present study, we describe the development of in vitro and in vivo models to study B. pseudomallei gastro...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Sanchez-Villamil, J. I., Tapia, D., Borlee, G. I., Borlee, B. R., Walker, D. H., Torres, A. G. Tags: Bacterial Infections Source Type: research

Lactic Acid Supplementation Increases Quantity and Quality of Gametocytes in Plasmodium falciparum Culture [Fungal and Parasitic Infections]
Malaria infection by Plasmodium falciparum continues to afflict millions of people worldwide, with transmission being dependent upon mosquito ingestion of the parasite gametocyte stage. These sexually committed stages develop from the asexual stages, yet the factors behind this transition are not completely understood. Here, we found that lactic acid increases gametocyte quantity and quality in P. falciparum culture. Low-passage-number NF54 parasites exposed to 8.2 mM lactic acid for various times were monitored using blood film gametocyte counts and RNA analysis throughout 2 weeks of gametocyte development in vitro for a ...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: West, R., Sullivan, D. J. Tags: Fungal and Parasitic Infections Source Type: research

The Extracellular Polysaccharide Matrix of Pseudomonas aeruginosa Biofilms Is a Determinant of Polymorphonuclear Leukocyte Responses [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Bacterial biofilms may cause chronic infections due to their ability to evade clearance by the immune system and antibiotics. The persistent biofilms induce a hyperinflammatory state that damages the surrounding host tissue. Knowledge about the components of biofilms that are responsible for provoking the harmful but inefficient immune response is limited. Flagella are known to stimulate the response of polymorphonuclear leukocytes (PMNs) to planktonic solitary bacteria. However, we provide evidence that flagella are not a prerequisite for the response of PMNs to Pseudomonas aeruginosa biofilms. Instead, we found that extr...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Rybtke, M., Jensen, P. O., Nielsen, C. H., Tolker-Nielsen, T. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Escherichia coli K12 Upregulates Programmed Cell Death Ligand 1 (PD-L1) Expression in Gamma Interferon-Sensitized Intestinal Epithelial Cells via the NF-{kappa}B Pathway [Host Response and Inflammation]
Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein which is used by tumor cells for immune evasion. PD-L1 is upregulated in inflamed intestinal tissues. The intestinal tract is colonized by millions of bacteria, most of which are commensal bacterial species. We hypothesized that under inflammatory conditions, some commensal bacterial species contribute to increased PD-L1 expression in intestinal epithelium and examined this hypothesis. Human intestinal epithelial HT-29 cells with and without interferon (IFN)- sensitization were incubated with six strains of four enteric bacterial species. The mRNA and p...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Lee, S. A., Wang, Y., Liu, F., Riordan, S. M., Liu, L., Zhang, L. Tags: Host Response and Inflammation Source Type: research

Bronchial Epithelial Tet2 Maintains Epithelial Integrity during Acute Pseudomonas aeruginosa Pneumonia [Bacterial Infections]
Respiratory epithelial cells are important for pulmonary innate immune responses during Pseudomonas aeruginosa infection. Tet methylcytosine dioxygenase 2 (Tet2) has been implicated in the regulation of host defense by myeloid and lymphoid cells, but whether Tet2 also contributes to epithelial responses during pneumonia is unknown. The aim of this study was to investigate the role of bronchial epithelial Tet2 in acute pneumonia caused by P. aeruginosa. To this end, we crossed mice with Tet2 flanked by two Lox-P sites (Tet2fl/fl mice) with mice expressing Cre recombinase under the bronchial epithelial cell-specific Cc10 pro...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Qin, W., Brands, X., van't Veer, C., de Vos, A. F., Scicluna, B. P., van der Poll, T. Tags: Bacterial Infections Source Type: research

Role of metAB in Methionine Metabolism and Optimal Chicken Colonization in Campylobacter jejuni [Molecular Pathogenesis]
Campylobacter jejuni is a zoonotic pathogen and is one of the leading causes of human gastroenteritis worldwide. C. jejuni IA3902 (representative of the sheep abortion clone) is genetically similar to C. jejuni W7 (representative of strain type NCTC 11168); however, there are significant differences in the ability of luxS mutants of these strains to colonize chickens. LuxS is essential for the activated methyl cycle and generates homocysteine for conversion to l-methionine. Comparative genomics identified differential distribution of the genes metA and metB, which function to convert homoserine for downstream production of...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Ruddell, B., Hassall, A., Sahin, O., Zhang, Q., Plummer, P. J., Kreuder, A. J. Tags: Molecular Pathogenesis Source Type: research

Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection [Microbial Immunity and Vaccines]
In this study, we tested whether a MAIT cell priming strategy could protect against aerosol Mycobacterium tuberculosis infection in mice. Intranasal costimulation with the lipopeptide Toll-like receptor (TLR)2/6 agonist, Pam2Cys (P2C), and the synthetic MR1 ligand, 5-OP-RU, resulted in robust expansion of MAIT cells in the lung. Although MAIT cell priming significantly enhanced MAIT cell activation and expansion early after M. tuberculosis challenge, these MAIT cells did not restrict M. tuberculosis bacterial load. MAIT cells were depleted by the onset of the adaptive immune response, with decreased detection of granzyme B...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Vorkas, C. K., Levy, O., Skular, M., Li, K., Aube, J., Glickman, M. S. Tags: Microbial Immunity and Vaccines Source Type: research

The Arg753Gln Polymorphism of Toll-Like Receptor 2 Has a Lower Occurrence in Patients with Syphilis, Suggesting Its Protective Effect in Czech and Slovak Individuals [Host-Associated Microbial Communities]
Syphilis is a bacterial infection caused by Treponema pallidum subsp. pallidum. Infection with T. pallidum subsp. pallidum and its dissemination lead to the synthesis of proinflammatory cytokines triggered by the interaction of bacterial lipoproteins with Toll-like receptor 2 (TLR2). TLR2 contains several nonsynonymous single-nucleotide polymorphisms that may impact the activation of its signaling cascade and alter the responsiveness to, or the course of, various infectious diseases, including those caused by pathogenic spirochetes. To investigate whether TLR2 polymorphism may influence susceptibility to syphilis, 221 heal...
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Grillova, L., Musilova, J., Janeckova, K., Pospisilova, P., Kuklova, I., Woznicova, V., Zakoucka, H., Smajs, D. Tags: Host-Associated Microbial Communities Source Type: research

Akkermansia muciniphila and Its Pili-Like Protein Amuc_1100 Modulate Macrophage Polarization in Experimental Periodontitis [Host Response and Inflammation]
This study demonstrates the putative therapeutic interest of the administration of A. muciniphila or Amuc_1100 in the management of periodontitis through their anti-inflammatory properties. (Source: Infection and Immunity)
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Mulhall, H., DiChiara, J. M., Deragon, M., Iyer, R., Huck, O., Amar, S. Tags: Host Response and Inflammation Source Type: research

Effects of Myeloid Hif-1{beta} Deletion on the Intestinal Microbiota in Mice under Environmental Hypoxia [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In conclusion, hypoxia caused heart enlargement, greater weight loss, and obvious microbial imbalance in myeloid Hif-1β-deficient mice. This study revealed genetic and microecological pathways for research on mechanisms of hypoxia. (Source: Infection and Immunity)
Source: Infection and Immunity - December 15, 2020 Category: Infectious Diseases Authors: Han, N., Pan, Z., Huang, Z., Chang, Y., Hou, F., Liu, G., Yang, R., Bi, Y. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research