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Infection and Immunity
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  • Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils
    Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils
  • Vamp3 Interacts with Multiple Chlamydial Inc Proteins
    Vamp3 Interacts with Multiple Chlamydial Inc Proteins
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Editorial

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    Rui Appelberg (1960–2020)
    Editorial
    Rui Appelberg (1960–2020)

Spotlight

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    Articles of Significant Interest in This Issue
    Spotlight
    Articles of Significant Interest in This Issue

Commentary

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    The Neutral Vaginal pH in Mice That Is Typical of Most Mammalian Species Should Not Deter Research Using Experimental Murine Models of <em>Candida</em> Vaginitis
    Commentary
    The Neutral Vaginal pH in Mice That Is Typical of Most Mammalian Species Should Not Deter Research Using Experimental Murine Models of Candida Vaginitis

    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.

    Paul L. Fidel

Minireview

  • Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils
    Minireview
    Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils

    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...

    Pragya Prasanna, Arun Upadhyay

Molecular Pathogenesis

  • The Role of <em>luxS</em> in <span class="named-content genus-species" id="named-content-1">Histophilus somni</span> Virulence and Biofilm Formation
    Molecular Pathogenesis
    The Role of luxS in Histophilus somni Virulence and Biofilm Formation

    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...

    Yu Pan, Shivakumara Siddaramappa, Indra Sandal, Allan Dickerman, Aloka B. Bandara, Thomas J. Inzana
  • The Pyocin Regulator PrtR Regulates Virulence Expression of <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway
    Molecular Pathogenesis
    The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway

    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.

    Hongying Jiao, Fan Li, Tietao Wang, Joey Kuok Hoong Yam, Liang Yang, Haihua Liang
  • Open Access
    The <span class="named-content genus-species" id="named-content-1">Yersinia pestis</span> GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague
    Molecular Pathogenesis
    The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague

    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.

    ...
    Samantha D. Crane, Srijon K. Banerjee, Kara R. Eichelberger, Richard C. Kurten, William E. Goldman, Roger D. Pechous
  • Bile Salts Differentially Enhance Resistance of Enterohemorrhagic <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> O157:H7 to Host Defense Peptides
    Molecular Pathogenesis
    Bile Salts Differentially Enhance Resistance of Enterohemorrhagic Escherichia coli O157:H7 to Host Defense Peptides

    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...

    Crystal Gadishaw-Lue, Alyssa Banaag, Sarah Birstonas, Aju-Sue Francis, Debora Barnett Foster

Cellular Microbiology: Pathogen-Host Cell Molecular Interactions

  • 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
    Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function

    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.

    George Papadopoulos, Robert Berland, Ashwini Sunkavalli, Stephen R. Coats, Richard P. Darveau, Caroline A. Genco
  • Open Access
    Eukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins
    Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
    Eukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins

    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.

    Duc-Cuong Bui, Lisa M. Jorgenson, Scot P. Ouellette, Elizabeth A. Rucks
  • cAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin
    Cellular Microbiology: Pathogen-Host Cell Molecular Interactions | Spotlight
    cAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin

    Cholera toxin (CT) is an AB5 protein toxin that activates the stimulatory alpha subunit of the heterotrimeric G protein (Gsα) through ADP-ribosylation. Activation of Gsα produces a cytopathic effect by stimulating adenylate cyclase and the production of cAMP.

    Tuhina Banerjee, Aby Grabon, Michael Taylor, Ken Teter
  • Adoptive Transfer of Group 3-Like Innate Lymphoid Cells Restores Mouse Colon Resistance to Colonization of a Gamma Interferon-Susceptible <span class="named-content genus-species" id="named-content-1">Chlamydia muridarum</span> Mutant
    Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
    Adoptive Transfer of Group 3-Like Innate Lymphoid Cells Restores Mouse Colon Resistance to Colonization of a Gamma Interferon-Susceptible Chlamydia muridarum Mutant

    The obligate intracellular bacterium Chlamydia muridarum can colonize the mouse colon for a long period, but a gamma interferon (IFN-γ)-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-γ but not in mice...

    Ying He, Hong Xu, Chenchen Song, John J. Koprivsek, Bernard Arulanandam, Huixiang Yang, Lijian Tao, Guangming Zhong
  • (p)ppGpp-Dependent Regulation of the Nucleotide Hydrolase PpnN Confers Complement Resistance in <span class="named-content genus-species" id="named-content-1">Salmonella enterica</span> Serovar Typhimurium
    Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
    (p)ppGpp-Dependent Regulation of the Nucleotide Hydrolase PpnN Confers Complement Resistance in Salmonella enterica Serovar Typhimurium

    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...

    N. Y Elizabeth Chau, Deyanira Pérez-Morales, Wael Elhenawy, Víctor H. Bustamante, Yong E. Zhang, Brian K. Coombes
  • Open Access
    Acid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections
    Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
    Acid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections

    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...

    Katrin Anne Becker, Rabea Verhaegh, Hedda-Luise Verhasselt, Simone Keitsch, Matthias Soddemann, Barbara Wilker, Gregory C. Wilson, Jan Buer, Syed A. Ahmad, Michael J. Edwards, Erich Gulbins

Bacterial Infections

  • Cardiotropic Isolates of <span class="named-content genus-species" id="named-content-1">Listeria monocytogenes</span> with Enhanced Vertical Transmission Dependent upon the Bacterial Surface Protein InlB
    Bacterial Infections
    Cardiotropic Isolates of Listeria monocytogenes with Enhanced Vertical Transmission Dependent upon the Bacterial Surface Protein InlB

    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...

    Nicole M. Lamond, P. David McMullen, Dhanendra Paramasvaran, Lavanya Visvahabrathy, Samuel J. Eallonardo, Akhil Maheswhari, Nancy E. Freitag
  • Targeting Neuropilin-1 Suppresses the Stability of CD4<sup>+</sup> CD25<sup>+</sup> Regulatory T Cells via the NF-κB Signaling Pathway in Sepsis
    Bacterial Infections
    Targeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-κB Signaling Pathway in Sepsis

    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...

    Yu-lei Gao, Chun-xue Wang, Zi-yi Wang, Wen-jie Li, Yan-cun Liu, Song-tao Shou, Yan-fen Chai
  • Gastric Metabolomics Detects <span class="named-content genus-species" id="named-content-1">Helicobacter pylori</span> Correlated Loss of Numerous Metabolites in Both the Corpus and Antrum
    Bacterial Infections
    Gastric Metabolomics Detects Helicobacter pylori Correlated Loss of Numerous Metabolites in Both the Corpus and Antrum

    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...

    Daniela Keilberg, Nina Steele, Sili Fan, Christina Yang, Yana Zavros, Karen M. Ottemann

Host Response and Inflammation

  • Free
    Exogenous Reproductive Hormones nor <span class="named-content genus-species" id="named-content-1">Candida albicans</span> Colonization Alter the Near Neutral Mouse Vaginal pH
    Host Response and Inflammation | Spotlight
    Exogenous Reproductive Hormones nor Candida albicans Colonization Alter the Near Neutral Mouse Vaginal pH

    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...

    Jian Miao, Hubertine M. E. Willems, Brian M. Peters
  • CXCR3-Dependent Immune Pathology in Mice following Infection with <span class="named-content genus-species" id="named-content-1">Toxoplasma gondii</span> during Early Pregnancy
    Host Response and Inflammation | Spotlight
    CXCR3-Dependent Immune Pathology in Mice following Infection with Toxoplasma gondii during Early Pregnancy

    Toxoplasmosis is a worldwide zoonosis caused by the obligate intracellular parasite Toxoplasma gondii. The symptoms of congenital toxoplasmosis range from embryonic death and resorption to subclinical infection, but the mechanism of disease onset remains unclear.

    Akari Nishida, Rina Ikeda, Hidefumi Furuoka, Yoshifumi Nishikawa

Microbial Immunity and Vaccines

  • Open Access
    Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Acute Murine Pneumonia
    Microbial Immunity and Vaccines | Spotlight
    Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia

    Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant...

    Emel Sen-Kilic, Catherine B. Blackwood, Annalisa B. Huckaby, Alexander M. Horspool, Kelly L. Weaver, Aaron C. Malkowski, William T. Witt, Justin R. Bevere, F. Heath Damron, Mariette Barbier
  • A Chimeric <span class="named-content genus-species" id="named-content-1">Plasmodium vivax</span> Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic <span class="named-content genus-species" id="named-content-2">P. cynomolgi</span> Berok Merozoites <em>In Vitro</em>
    Microbial Immunity and Vaccines
    A Chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro

    Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing P. vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-...

    Fei-hu Shen, Jessica Jie Ying Ong, Yi-fan Sun, Yao Lei, Rui-lin Chu, Kokouvi Kassegne, Hai-tian Fu, Cheng Jin, Eun-Taek Han, Bruce Russell, Jin-Hee Han, Yang Cheng

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Infection and Immunity: 89 (2)

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  • Pathogenic Mannheimia haemolytica Invades Differentiated Bovine Airway Epithelial Cells
  • Fitness Trade-Offs Resulting from Bacteriophage Resistance Potentiate Synergistic Antibacterial Strategies
  • An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
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