Brucella ovis Cysteine Biosynthesis Contributes to Peroxide Stress Survival and Fitness in the Intracellular Niche [Bacterial Infections]
Brucella ovis is an ovine intracellular pathogen with tropism for the male genital tract. To establish and maintain infection, B. ovis must survive stressful conditions inside host cells, including low pH, nutrient limitation, and reactive oxygen species. The same conditions are often encountered in axenic cultures during stationary phase. Studies of stationary phase may thus inform our understanding of Brucella infection biology, yet the genes and pathways that are important in Brucella stationary-phase physiology remain poorly defined. We measured fitness of a barcoded pool of B. ovis Tn-himar mutants as a function of gr...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Varesio, L. M., Fiebig, A., Crosson, S. Tags: Bacterial Infections Source Type: research

Human Corneal Epithelial Cells Internalize Aspergillus flavus Spores by Actin-Mediated Endocytosis [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Human corneal epithelial (HCE) cells play a significant role in the innate immune response by secreting cytokines and antimicrobial peptides when they encounter fungal pathogens. But the detailed mechanism of attachment and engulfment of the fungal conidia by HCE cells is not well understood. Here, we show the phagocytosis of Aspergillus flavus conidia by RCB2280 cells and primary HCE cultures using confocal microscopy and proteomic analysis of conidium-containing phagosomes. Phalloidin staining showed actin polymerization, leading to an actin ring around engulfed conidia. Cytochalasin D inhibited the actin-mediated endocy...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Arunachalam, D., Namperumalsamy, V. P., Prajna, L., Kuppamuthu, D. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology [Molecular Pathogenesis]
Relapsing fever (RF), caused by spirochetes of the genus Borrelia, is a globally distributed, vector-borne disease with high prevalence in developing countries. To date, signaling pathways required for infection and virulence of RF Borrelia spirochetes are unknown. Cyclic di-AMP (c-di-AMP), synthesized by diadenylate cyclases (DACs), is a second messenger predominantly found in Gram-positive organisms that is linked to virulence and essential physiological processes. Although Borrelia is Gram-negative, it encodes one DAC (CdaA), and its importance remains undefined. To investigate the contribution of c-di-AMP signaling in ...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Jackson-Litteken, C. D., Ratliff, C. T., Kneubehl, A. R., Siletti, C., Pack, L., Lan, R., Huynh, T. N., Lopez, J. E., Blevins, J. S. Tags: Molecular Pathogenesis Source Type: research

Polymorphonuclear Myeloid-Derived Cells That Contribute to the Immune Paralysis Are Generated in the Early Phase of Sepsis via PD-1/PD-L1 Pathway [Host Response and Inflammation]
This study investigated the contribution of MDCs to immune paralysis. Treatment of mice with zymosan (ZM) induced a marked increase in the total number of splenocytes with an increase in the proportion of Gr-1hi cells and a decrease in the proportion of T cells on day 7; levels of these cells eventually return to levels similar to those of control mice on day 21. T-cell activation and gamma interferon (IFN-) expression by CD8+ T cells were clearly impaired in ZM-treated mice on day 21 (d21-ZM mice). Gr-1hi cells showed a CD11b+ Ly6Ghi polymorphonuclear phenotype. Injection of lipopolysaccharide (LPS) into d21-ZM mice impai...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Ao, X., Yang, Y., Okiji, T., Azuma, M., Nagai, S. Tags: Host Response and Inflammation Source Type: research

Roles of OmpX, an Outer Membrane Protein, on Virulence and Flagellar Expression in Uropathogenic Escherichia coli [Molecular Pathogenesis]
Uropathogenic Escherichia coli (UPEC) is a major pathogen that causes urinary tract infection (UTI). This bacterium adheres to and internalizes within urinary tract cells, where it aggregates and subsequently forms biofilm-like multicellular colonies that protect UPEC from antimicrobial agents and the host’s immune system. Here, we show that OmpX, an outer membrane protein, plays a role in the pathogenesis of UPEC in renal cells. Deletion of ompX decreased bacterial internalization and aggregation within kidney epithelial cells and also impaired the colonization of mouse urinary tracts, but the ompX mutant still adhe...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Hirakawa, H., Suzue, K., Takita, A., Kamitani, W., Tomita, H. Tags: Molecular Pathogenesis Source Type: research

Sulfate Import in Salmonella Typhimurium Impacts Bacterial Aggregation and the Respiratory Burst in Human Neutrophils [Host Response and Inflammation]
During enteric salmonellosis, neutrophil-generated reactive oxygen species alter the gut microenvironment, favoring survival of Salmonella Typhimurium. While type 3 secretion system 1 (T3SS-1) and flagellar motility are potent Salmonella Typhimurium agonists of the neutrophil respiratory burst in vitro, neither of these pathways alone is responsible for stimulation of a maximal respiratory burst. To identify Salmonella Typhimurium genes that impact the magnitude of the neutrophil respiratory burst, we performed a two-step screen of defined mutant libraries in coculture with human neutrophils. We first screened Salmonella T...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Westerman, T. L., Sheats, M. K., Elfenbein, J. R. Tags: Host Response and Inflammation Source Type: research

Sialic Acid Protects Nontypeable Haemophilus influenzae from Natural IgM and Promotes Survival in Murine Respiratory Tract [Molecular Pathogenesis]
Nontypeable Haemophilus influenzae (NTHi), a common inhabitant of the human nasopharynx and upper airways, causes opportunistic respiratory tract infections that are frequently recurring and chronic. NTHi utilizes sialic acid from the host to evade antibacterial defenses and persist in mucosal tissues; however, the role of sialic acid scavenged by NTHi during infection is not fully understood. We previously showed that sialylation protects specific epitopes on NTHi lipooligosaccharide (LOS) targeted by bactericidal IgM in normal human serum. Here, we evaluated the importance of immune evasion mediated by LOS sialylation in...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Jackson, M. D., Wong, S. M., Akerley, B. J. Tags: Molecular Pathogenesis Source Type: research

Does Antibody Avidity to Plasmodium falciparum Merozoite Antigens Increase with Age in Individuals Living in Malaria-Endemic Areas? [Fungal and Parasitic Infections]
High-avidity antibodies (Abs) are acquired after a few Plasmodium falciparum infections in low transmission areas, but it remains unclear if Ab avidity to different merozoite antigens increases with age in individuals with persistent antigenemia and, if so, when a fully mature Ab response occurs. The study used plasma samples collected between 1996 and 1998 from 566 individuals aged 4 to 84 years in Simbok, Cameroon, where residents received an estimated 1.6 infectious mosquito bites/person/night. Plasma samples were examined for Ab levels (median fluorescence intensity [MFI]) and Ab avidity index (AI) (where AI = [MFI aft...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Tassi Yunga, S., Bobbili, N., Lloyd, Y. M., Antallan, J., Matsunaga, M., Quakyi, I., Leke, R. F. G., Taylor, D. W. Tags: Fungal and Parasitic Infections Source Type: research

Articles of Significant Interest in This Issue [Spotlight]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Tags: Spotlight Source Type: research

IFN-{gamma}-/- Mice Resist Actinobacillus pleuropneumoniae Infection by Promoting Early Lung IL-18 Release and PMN-I Accumulation [Host Response and Inflammation]
This study identifies IFN- as a target for regulating the inflammatory response in the lung and provides a basis for understanding the course of clinical bacterial pneumonia and for the formulation of treatment protocols. (Source: Infection and Immunity)
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Bao, C., Liu, B., Zhu, R., Xiao, J., Li, Z., Jiang, H., Wang, B., Langford, P. R., Fei, R., Li, N., Lei, L. Tags: Host Response and Inflammation Source Type: research

Increased Pulmonary Pneumococcal Clearance after Resolution of H9N2 Avian Influenza Virus Infection in Mice [Bacterial Infections]
H9N2 avian influenza virus has been continuously circulating among poultry and can infect mammals, indicating that this virus is a potential pandemic strain. During influenza pandemics, secondary bacterial (particularly pneumococcal) pneumonia usually contributes to excessive mortality. In the present study, we observed the dynamic effect of H9N2 virus infection on host defense against secondary pneumococcal infection in mice. BALB/c mice were intranasally inoculated with 1.2 x 105 PFU of H9N2 virus followed by 1 x 106 CFU of Streptococcus pneumoniae at 7, 14, or 28 days post-H9N2 infection (dpi). The bacterial load, histo...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Li, J., Wang, H., Lian, P., Bai, Y., Zhang, Z., Zhao, L., Xu, T., Qiao, J. Tags: Bacterial Infections Source Type: research

FBPAII and rpoBC, the Two Novel Secreted Proteins Identified by the Proteomic Approach from a Comparative Study between Antibiotic-Sensitive and Antibiotic-Resistant Helicobacter pylori-Associated Gastritis Strains [Molecular Pathogenesis]
This report is the first to demonstrate the association of these two novel secreted proteins, namely, rpoBC and FBPAII, with antibiotic-sensitive H. pylori-associated gastritis strains. (Source: Infection and Immunity)
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Kittisenachai, S., Rojpibulstit, P., Vilaichone, R.-K., Gamnarai, P., Phaonakrop, N., Suealek, N. Tags: Molecular Pathogenesis Source Type: research

Lymphotoxin {beta} Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii [Host Response and Inflammation]
This study uncovers the decisive role of the LTβR in cytokine regulation and adaptive immune responses to control T. gondii. (Source: Infection and Immunity)
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Tersteegen, A., Sorg, U. R., Virgen-Slane, R., Helle, M., Petzsch, P., Dunay, I. R., Köhrer, K., Degrandi, D., Ware, C. F., Pfeffer, K. Tags: Host Response and Inflammation Source Type: research

Ostertagia ostertagi Mediates Early Host Immune Responses via Macrophage and Toll-Like Receptor Pathways [Host Response and Inflammation]
Ostertagia ostertagi is an abomasal parasite with significant economic impact on the cattle industry. Early host immune responses are poorly understood. Here, we examined time course expression of Toll-like receptors (TLRs) in peripheral blood mononuclear cells (PBMC) during infection where PBMC macrophages (M) generated both pro- and anti-inflammatory responses when incubated with excretory/secretory products (ESP) from fourth-stage larvae (OoESP-L4) or adult worms (OoESP-Ad). First, changes in cell morphology clearly showed that both OoESP-L4 and OoESP-Ad activated PBMC-M in vitro, resulting in suppressed CD40 and increa...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Bakshi, M., Hebert, D., Gulbronson, C., Bauchan, G., Tuo, W., Zarlenga, D. Tags: Host Response and Inflammation Source Type: research

Host Genome-Wide Association Study of Infant Susceptibility to Shigella-Associated Diarrhea [Host Response and Inflammation]
Shigella is a leading cause of moderate-to-severe diarrhea globally and the causative agent of shigellosis and bacillary dysentery. Associated with 80 to 165 million cases of diarrhea and>13% of diarrheal deaths, in many regions, Shigella exposure is ubiquitous while infection is heterogenous. To characterize host-genetic susceptibility to Shigella-associated diarrhea, we performed two independent genome-wide association studies (GWAS) including Bangladeshi infants from the PROVIDE and CBC birth cohorts in Dhaka, Bangladesh. Cases were infants with Shigella-associated diarrhea (n = 143) and controls were infants with no...
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Authors: Duchen, D., Haque, R., Chen, L., Wojcik, G., Korpe, P., Nayak, U., Mentzer, A. J., Kirkpatrick, B., Petri, W. A., Duggal, P. Tags: Host Response and Inflammation Source Type: research

Editorial Board [Masthead]
(Source: Infection and Immunity)
Source: Infection and Immunity - May 17, 2021 Category: Infectious Diseases Tags: Masthead Source Type: research

RNA Sequencing Reveals Distinct Immune Responses in the Chorioamniotic Membranes of Women with Preterm Labor and Microbial or Sterile Intra-amniotic Inflammation [Host Response and Inflammation]
Preterm labor precedes premature birth, the leading cause of neonatal morbidity and mortality worldwide. Preterm labor can occur in the context of either microbe-associated intra-amniotic inflammation (i.e., intra-amniotic infection) or intra-amniotic inflammation in the absence of detectable microorganisms (i.e., sterile intra-amniotic inflammation). Both intra-amniotic infection and sterile intra-amniotic inflammation trigger local immune responses that have deleterious effects on fetal life. Yet, the extent of such immune responses in the fetal tissues surrounding the amniotic cavity (i.e., the chorioamniotic membranes)...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Motomura, K., Romero, R., Galaz, J., Tarca, A. L., Done, B., Xu, Y., Leng, Y., Garcia-Flores, V., Arenas-Hernandez, M., Theis, K. R., Gershater, M., Jung, E., Hsu, C.-D., Gomez-Lopez, N. Tags: Host Response and Inflammation Source Type: research

mRNA Transcriptome Analysis of Bone in a Mouse Model of Implant-Associated Staphylococcus aureus Osteomyelitis [Host Response and Inflammation]
To investigate the molecular pathogenesis of bone with osteomyelitis, we developed implant-associated osteomyelitis (IAOM) models in mice. An orthopedic stainless pin was surgically placed in the right femoral midshaft of mice, followed by an inoculation of Staphylococcus aureus into the medullary cavity. Typical characteristics of IAOM, like periosteal reaction and intraosseous abscess, occurred by day 14 postinfection. By day 28 postinfection, necrotic abscess, sequestrum formation, and deformity of the whole femur were observed. Transcriptional analysis identified 101 and 1,702 differentially expressed genes (DEGs) betw...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Lin, Y., Su, J., Wang, Y., Xu, D., Zhang, X., Yu, B. Tags: Host Response and Inflammation Source Type: research

Staphylococcus aureus Tet38 Efflux Pump Structural Modeling and Roles of Essential Residues in Drug Efflux and Host Cell Internalization [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
The Staphylococcus aureus Tet38 membrane protein has distinct functions, including drug efflux and host cell attachment and internalization mediated by interaction with host cell CD36. Using structural modeling and site-directed mutagenesis, we identified key amino acids involved in different functions. Tet38, a member of the major facilitator superfamily, is predicted to have 14 transmembrane segments (TMS), 6 cytoplasmic loops, and 7 external loops. Cysteine substitutions of arginine 106 situated at the junction of TMS 4 and external loop L2, and glycine 151 of motif C on TMS 5, resulted in complete or near-complete (8- ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Truong-Bolduc, Q. C., Wang, Y., Hooper, D. C. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Listeria monocytogenes MenI Encodes a DHNA-CoA Thioesterase Necessary for Menaquinone Biosynthesis, Cytosolic Survival, and Virulence [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Listeria monocytogenes is a Gram-positive, intracellular pathogen that is highly adapted to invade and replicate in the cytosol of eukaryotic cells. Intermediate metabolites in the menaquinone biosynthesis pathway are essential for the cytosolic survival and virulence of L. monocytogenes, independent of the production of menaquinone (MK) and aerobic respiration. Determining which specific intermediate metabolite(s) are essential for cytosolic survival and virulence has been hindered by the lack of an identified 1,4-dihydroxy-2-naphthoyl-coenzyme A (DHNA-CoA) thioesterase essential for converting DHNA-CoA to DHNA in the MK ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Smith, H. B., Li, T. L., Liao, M. K., Chen, G. Y., Guo, Z., Sauer, J.-D. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection [Host-Associated Microbial Communities]
In this study, we investigate the role(s) of lipid metabolism in mammary cells during Streptococcus uberis infection. Our results indicate that S. uberis induces the synthesis of fatty acids and production of LDs. Importantly, taurine reduces fatty acid synthesis, the abundance of LDs and the in vitro bacterial load of S. uberis. These changes are mediated, at least partly, by the E3 ubiquitin ligase IDOL, which is associated with the degradation of low-density lipoprotein receptors (LDLRs). We have identified a critical role for IDOL-mediated fatty acid synthesis in bacterial infection, and we suggest that taurine may be ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Wan, Z., Lan, R., Zhou, Y., Xu, Y., Wang, Z., Luo, Z., Miao, J. Tags: Host-Associated Microbial Communities Source Type: research

Active Hexose-Correlated Compound Restores Gene Expression and Protein Secretion of Protective Cytokines of Immune Cells in a Murine Stress Model during Chlamydia muridarum Genital Infection [Bacterial Infections]
This study evaluated infection and changes in immunological parameters of stressed AHCC-fed mice with or without C. muridarum genital infection. We hypothesized that AHCC feeding to stressed mice restores protective immune function and reduces susceptibility to C. muridarum genital infection. The results show that oral feeding of stressed mice with AHCC resulted in decreased shedding of C. muridarum from the genital tract, reduced production of plasma catecholamines, increased expression of T-bet and reduced GATA-3 in CD4+ T cells, increased production of interleukin-12 (IL-12) and interferon gamma (IFN-) and reduced produ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Belay, T., Sahu, R., Martin, E., Brown, K., Rolen, C., Hankins, S., Punturi, B., Patterson, M., Chambers, C., Kirby, B., Butchar, J. Tags: Bacterial Infections Source Type: research

Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection [Microbial Immunity and Vaccines]
Streptococcus pneumoniae remains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most serotypes included in vaccines, a rise in infection due to nonvaccine serotypes and moderate efficacy against some vaccine serotypes have contributed to high disease incidence. Additionally, numerous isolates of S. pneumoniae are antibiotic or multidrug resistant. Several conserved pneumococcal proteins prevalent in the majority of serotypes have been examined for their potential as vaccines in preclinical and clinical trials. An additional, yet-unexp...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Huang, J., Gingerich, A. D., Royer, F., Paschall, A. V., Pena-Briseno, A., Avci, F. Y., Mousa, J. J. Tags: Microbial Immunity and Vaccines Source Type: research

Loss of Interleukin-10 (IL-10) Signaling Promotes IL-22-Dependent Host Defenses against Acute Clostridioides difficile Infection [Host Response and Inflammation]
In this report, we employed Il10–/– mice as a model of spontaneous colitis to examine the impact of constitutive intestinal immune activation, independent of infection, on C. difficile disease pathogenesis. Upon C. difficile challenge, Il10–/– mice exhibited significantly decreased morbidity and mortality compared to littermate Il10 heterozygote (Il10HET) control mice, despite a comparable C. difficile burden, innate immune response, and microbiota composition following infection. Similarly, antibody-mediated blockade of interleukin-10 (IL-10) signaling in wild-type C57BL/6 mice conveyed a survival ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Cribas, E. S., Denny, J. E., Maslanka, J. R., Abt, M. C. Tags: Host Response and Inflammation Source Type: research

Sialidase of Glaesserella parasuis Augments Inflammatory Response via Desialylation and Abrogation of Negative Regulation of Siglec-5 [Molecular Pathogenesis]
This study helps to understand the molecular mechanism underlying the inflammatory response induced by sialidase secreted by G. parasuis and the acute inflammation caused by G. parasuis. (Source: Infection and Immunity)
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Song, Y., Pan, Q., Xiao, J., Li, W., Ma, H., Chen, H., Cai, X., Xu, X. Tags: Molecular Pathogenesis Source Type: research

Purinergic P2X7 Receptor Mediates the Elimination of Trichinella spiralis by Activating NF-{kappa}B/NLRP3/IL-1{beta} Pathway in Macrophages [Fungal and Parasitic Infections]
In this study, we aimed to investigate the role of P2X7R in the activation of NLRP3 in macrophages during the intestinal immune response against T. spiralis. We found that T. spiralis infection upregulated expression of P2X7R and activation of NLRP3 in macrophages in mice. In vivo, P2X7R deficiency resulted in increased intestinal adult and muscle larval burdens, along with decreased expression of NLRP3/interleukin-1β (IL-1β) in macrophages from the infected mice with T. spiralis. In In vitro experiments, P2X7R blockade inhibited activation of NLRP3/IL-1β via NF-B and thus reduced the capacity of macrophages...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Guan, F., Jiang, W., Bai, Y., Hou, X., Jiang, C., Zhang, C., Jacques, M. L., Liu, W., Lei, J. Tags: Fungal and Parasitic Infections Source Type: research

Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection [Bacterial Infections]
Enterococcus faecalis infections are considered a major public health concern worldwide. The complement system has a crucial role in the protection against different microbial pathogens, including E. faecalis. Complement can be activated through three different pathways, including the classical, lectin, and alternative pathways. There is limited information on the role of the classical pathway (CP) in protection against infections caused by E. faecalis. In the present study, we generated Fab fragments that successfully block the CP in mouse via inhibition of a key enzyme, C1s-A. Our results showed that anti-C1s-A Fab fragm...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Shehab El-Din, E. M. R., Elgaml, A., Ali, Y. M., Hassan, R. Tags: Bacterial Infections Source Type: research

Distinct Group B Streptococcus Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells. Here, we expanded on these studies by utilizing the same set of genetical...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Flaherty, R. A., Aronoff, D. M., Gaddy, J. A., Petroff, M. G., Manning, S. D. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research

The Complex Link between the Female Genital Microbiota, Genital Infections, and Inflammation [Minireviews]
The female genital tract microbiota is part of a complex ecosystem influenced by several physiological, genetic, and behavioral factors. It is uniquely linked to a woman’s mucosal immunity and plays a critical role in the regulation of genital inflammation. A vaginal microbiota characterized by a high abundance of lactobacilli and low overall bacterial diversity is associated with lower inflammation. On the other hand, a more diverse microbiota is linked to high mucosal inflammation levels, a compromised genital epithelial barrier, and an increased risk of sexually transmitted infections and other conditions. Several...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Dabee, S., Passmore, J.-A. S., Heffron, R., Jaspan, H. B. Tags: Minireviews Source Type: research

Im Infected, Eat Me! Innate Immunity Mediated by Live, Infected Cells Signaling To Be Phagocytosed [Minireviews]
Innate immunity against pathogens is known to be mediated by barriers to pathogen invasion, activation of complement, recruitment of immune cells, immune cell phagocytosis of pathogens, death of infected cells, and activation of the adaptive immunity via antigen presentation. Here, we propose and review evidence for a novel mode of innate immunity whereby live, infected host cells induce phagocytes to phagocytose the infected cell, thereby potentially reducing infection. We discuss evidence that host cells, infected by virus, bacteria, or other intracellular pathogens (i) release nucleotides and chemokines as find-me signa...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Birkle, T., Brown, G. C. Tags: Minireviews Source Type: research

Response of Leucine-Rich Repeat Domain-Containing Protein in Haemaphysalis longicornis to Babesia microti Infection and Its Ligand Identification [Fungal and Parasitic Infections]
In this study, one of the ligands for LRR from H. longicornis (HlLRR) was identified in Babesia microti, designated BmActin, using glutathione transferase (GST) pulldown experiments and immunofluorescence assays. Moreover, RNA interference of HlLRR led to a decrease in the BmActin mRNA expression in the midgut of fully engorged ticks which fed on B. microti-infected mice. We also found that the expression level of the innate immune molecules in H. longicornis, defensin, antimicrobial peptides (AMPs), and lysozyme, were downregulated after the knockdown of HlLRR. However, subolesin expression was upregulated. These results ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Yao, J., Xu, Z., Sun, Z., Zhou, K., Lu, J., Mi, R., Huang, Y., Han, X., Ren, K., Chen, Z., Gong, H. Tags: Fungal and Parasitic Infections Source Type: research

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

Contribution of Noncanonical Antigens to Virulence and Adaptive Immunity in Human Infection with Enterotoxigenic E. coli [Microbial Immunity and Vaccines]
Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-apertur...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Kuhlmann, F. M., Laine, R. O., Afrin, S., Nakajima, R., Akhtar, M., Vickers, T., Parker, K., Nizam, N. N., Grigura, V., Goss, C. W., Felgner, P. L., Rasko, D. A., Qadri, F., Fleckenstein, J. M. Tags: Microbial Immunity and Vaccines Source Type: research

In Vivo and In Vitro Impairments in T Helper Cell and Neutrophil Responses against Mucor irregularis in Card9 Knockout Mice [Fungal and Parasitic Infections]
Mucor irregularis is a frequently found fungus in Asia, especially China, and it causes primary cutaneous mucormycosis with a high rate of disfigurement. Caspase recruitment domain-containing protein 9 (Card9) is an essential adaptor molecule downstream of C-type lectin receptors. It mediates the activation of nuclear factor kappa B (NF-B), regulates T helper 1 (Th1) and Th17 differentiation, and plays an important role in fungal immune surveillance. CARD9 deficiency correlates with the increased susceptibility to many fungal infections, including cutaneous mucormycosis caused by M. irregularis. However, the underlying imm...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Sun, L., Zhang, S., Wan, Z., Li, R., Yu, J. Tags: Fungal and Parasitic Infections Source Type: research

Evaluating the Role of STAT3 in CD4+ T Cells in Susceptibility to Invasive Aspergillosis [Fungal and Parasitic Infections]
We aimed to determine whether T cell-specific STAT3 deletion influences the immune response to Aspergillus in the immunosuppressed context in CD4Stat3–/– mice. Immunosuppressed and nonimmunosuppressed CD4Stat3–/– mice and littermate Stat3flox/flox (Stat3fl/fl) mice were infected with Aspergillus fumigatus in an aerosol chamber, and the weight, activity, appearance, and respiratory rate of the mice were monitored daily for 21 days to evaluate their survival. Aspergillus infection was confirmed by lung fungal culture counts, histology, and a galactomannan test. Cytokines were measured at 3 days postin...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Gohir, W., McTaggart, L., Kus, J. V., Mazzulli, T., Kumar, D., Humar, A., Husain, S. Tags: Fungal and Parasitic Infections Source Type: research

Differential Outcome between BALB/c and C57BL/6 Mice after Escherichia coli O157:H7 Infection Is Associated with a Dissimilar Tolerance Mechanism [Host Response and Inflammation]
Enterohemorrhagic Escherichia coli (EHEC) infections can result in a wide range of clinical presentations despite that EHEC strains belong to the O157:H7 serotype, one of the most pathogenic forms. Although pathogen virulence influences disease outcome, we emphasize the concept of host-pathogen interactions, which involve resistance or tolerance mechanisms in the host that determine total host fitness and bacterial virulence. Taking advantage of the genetic differences between mouse strains, we analyzed the clinical progression in C57BL/6 and BALB/c weaned mice infected with an E. coli O157:H7 strain. We carefully analyzed...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Bernal, A. M., Fernandez-Brando, R. J., Bruballa, A. C., Fiorentino, G. A., Pineda, G. E., Zotta, E., Vermeulen, M., Ramos, M. V., Rumbo, M., Palermo, M. S. Tags: Host Response and Inflammation Source Type: research

RIPK3 Facilitates Host Resistance to Oral Toxoplasma gondii Infection [Fungal and Parasitic Infections]
In this study, we further defined the role of Z-DNA binding protein 1 (ZBP1) as a PRR and assessed its contribution to necroptosis as a host protection mechanism to T. gondii infection. We found that ZBP1 does not induce proinflammatory necroptosis cell death, and ZBP1 null mice have reduced survival after oral T. gondii infection. In contrast, mice deleted in receptor-interacting serine/threonine-protein kinase 3 (RIPK3–/–), a central mediator of necroptosis, have significantly improved survival after oral T. gondii infection without a reduction in parasite burden. The physiological consequences of RIPK3 activ...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Cervantes, P. W., Martorelli Di Genova, B., Erazo Flores, B. J., Knoll, L. J. Tags: Fungal and Parasitic Infections Source Type: research

The KbvR Regulator Contributes to Capsule Production, Outer Membrane Protein Biosynthesis, Antiphagocytosis, and Virulence in Klebsiella pneumoniae [Molecular Pathogenesis]
Klebsiella pneumoniae is an opportunistic pathogen that mostly affects patients with weakened immune systems, but a few serotypes (especially K1 and K2) are highly invasive and result in systemic infection in healthy persons. The ability to evade and survive the components of the innate immune system is critical in infection. To investigate the role and mechanism of transcription regulator KP1_RS12260 (KbvR) in virulence and defense against the innate immune response, kbvR deletion mutant and complement strains were constructed. The in vivo animal infection assay and in vitro antiphagocytosis assay demonstrate K. pneumonia...
Source: Infection and Immunity - April 16, 2021 Category: Infectious Diseases Authors: Xu, L., Wang, M., Yuan, J., Wang, H., Li, M., Zhang, F., Tian, Y., Yang, J., Wang, J., Li, B. Tags: Molecular Pathogenesis Source Type: research

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

Getting Your Neutrophil: Neutrophil Transepithelial Migration in the Lung [Minireviews]
Neutrophil transepithelial migration is a fundamental process that facilitates the rapid trafficking of neutrophils to inflammatory foci and occurs across a diverse range of tissues. For decades, there has been widespread interest in understanding the mechanisms that drive this migratory process in response to different pathogens and organ systems. This has led to the successful integration of key findings on neutrophil transepithelial migration from the intestines, lungs, liver, genitourinary tract, and other tissues into a single, cohesive model. However, recent studies have identified organ-specific differences in neutr...
Source: Infection and Immunity - March 19, 2021 Category: Infectious Diseases Authors: Adams, W., Espicha, T., Estipona, J. Tags: Minireviews Source Type: research

Polymicrobial Interactions in the Urinary Tract: Is the Enemy of My Enemy My Friend? [Minireviews]
The vast majority of research pertaining to urinary tract infection has focused on a single pathogen in isolation and predominantly Escherichia coli. However, polymicrobial urine colonization and infections are prevalent in several patient populations, including individuals with urinary catheters. The progression from asymptomatic colonization to symptomatic infection and severe disease is likely shaped by interactions between traditional pathogens, as well as constituents of the normal urinary microbiota. Recent studies have begun to experimentally dissect the contribution of polymicrobial interactions to disease outcomes...
Source: Infection and Immunity - March 19, 2021 Category: Infectious Diseases Authors: Gaston, J. R., Johnson, A. O., Bair, K. L., White, A. N., Armbruster, C. E. Tags: Minireviews Source Type: research

A SNP in the Cache 1 Signaling Domain of Diguanylate Cyclase STM1987 Leads to Increased In Vivo Fitness of Invasive Salmonella Strains [Molecular Genomics]
In this study, we identified a SNP in the cache 1 signaling domain of diguanylate cyclase STM1987 in the invasive Salmonella enterica serovar Typhimurium type strain D23580. This SNP was conserved in 118 other iNTS strains analyzed and was comparatively absent in global S. Typhimurium isolates associated with gastroenteritis. STM1987 catalyzes the formation of bis-(3',5')-cyclic dimeric GMP (c-di-GMP) and is proposed to stimulate production of cellulose independent of the master biofilm regulator CsgD. We show that the amino acid change in STM1987 leads to a 10-fold drop in cellulose production and increased fitness in a m...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Sokaribo, A. S., Balezantis, L. R., MacKenzie, K. D., Wang, Y., Palmer, M. B., Chung, B., Herman, N. J., McCarthy, M. C., Chen, J. M., White, A. P. Tags: Molecular Genomics Source Type: research

Hemoglobin Induces Early and Robust Biofilm Development in Streptococcus pneumoniae by a Pathway That Involves comC but Not the Cognate comDE Two-Component System [Molecular Pathogenesis]
Streptococcus pneumoniae grows in biofilms during both asymptomatic colonization and infection. Pneumococcal biofilms on abiotic surfaces exhibit delayed growth and lower biomass and lack the structures seen on epithelial cells or during nasopharyngeal carriage. We show here that adding hemoglobin to the medium activated unusually early and vigorous biofilm growth in multiple S. pneumoniae serotypes grown in batch cultures on abiotic surfaces. Human blood (but not serum, heme, or iron) also stimulated biofilms, and the pore-forming pneumolysin, ply, was required for this induction. S. pneumoniae transitioning from plankton...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Akhter, F., Womack, E., Vidal, J. E., Le Breton, Y., McIver, K. S., Pawar, S., Eichenbaum, Z. Tags: Molecular Pathogenesis Source Type: research

Cutibacterium acnes: the Urgent Need To Identify Diagnosis Markers [Commentary]
Cutibacterium acnes role is well described during acne but remains a mystery regarding its implication in bone and prosthesis or cerebrospinal fluid shunt infections. The main issue is that these low-grade symptom infections are difficult to diagnose and lead to irreversible and grave sequelae for patients. Consequently, there is an urgent need to find new biomarkers to accelerate the diagnosis of disease, an issue addressed by Beaver et al. thanks to a promising proteomic approach. (Source: Infection and Immunity)
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Mongaret, C., Velard, F., Reffuveille, F. Tags: Commentary Source Type: research

Ectopic Expression of Human Thymosin {beta}4 Confers Resistance to Legionella pneumophila during Pulmonary and Systemic Infection in Mice [Bacterial Infections]
Thymosin beta-4 (Tβ4) is an actin-sequestering peptide that plays important roles in regeneration and remodeling of injured tissues. However, its function in a naturally occurring pathogenic bacterial infection model has remained elusive. We adopted Tβ4-overexpressing transgenic (Tg) mice to investigate the role of Tβ4 in acute pulmonary infection and systemic sepsis caused by Legionella pneumophila. Upon infection, Tβ4-Tg mice demonstrated significantly lower bacterial loads in the lung, less hyaline membranes and necrotic abscess, with lower interstitial infiltration of neutrophils, CD4+, and CD8+ T c...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Park, B., Shin, M. H., Kim, J., Park, G., Ryu, Y.-K., Lee, J.-W., Kim, T. J., Moon, E.-Y., Lee, K.-M. Tags: Bacterial Infections Source Type: research

The Increased Accumulation of Staphylococcus aureus Virulence Factors Is Maximized in a purR Mutant by the Increased Production of SarA and Decreased Production of Extracellular Proteases [Molecular Pathogenesis]
Mutation of purR was previously shown to enhance the virulence of Staphylococcus aureus in a murine sepsis model, and this cannot be fully explained by increased expression of genes within the purine biosynthesis pathway. Rather, the increased production of specific S. aureus virulence factors, including alpha toxin and the fibronectin-binding proteins, was shown to play an important role. Mutation of purR was also shown previously to result in increased abundance of SarA. Here, we demonstrate by transposon sequencing that mutation of purR in the USA300 strain LAC increases fitness in a biofilm while mutation of sarA has t...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Alkam, D., Jenjaroenpun, P., Ramirez, A. M., Beenken, K. E., Spencer, H. J., Smeltzer, M. S. Tags: Molecular Pathogenesis Source Type: research

Sex Differences in Population Dynamics during Formation of Kidney Bacterial Communities by Uropathogenic Escherichia coli [Host-Associated Microbial Communities]
In this study, we aimed to understand UPEC population dynamics during ascending pyelonephritis, namely, formation of kidney bacterial communities (KBCs) in the renal tubular lumen and nucleation of renal abscesses. We inoculated the bladders of both male and female C3H/HeN mice, a background which features vesicoureteral reflux; we have previously shown that in this model, males develop severe, high-titer pyelonephritis and renal abscesses much more frequently than females. Mice were infected with 40 isogenic, PCR-tagged ("barcoded") UPEC strains, and tags remaining in bladder and kidneys were ascertained at inte...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: McLellan, L. K., Daugherty, A. L., Hunstad, D. A. Tags: Host-Associated Microbial Communities Source Type: research

Analysis of Staphylococcus aureus Transcriptome in Pediatric Soft Tissue Abscesses and Comparison to Murine Infections [Bacterial Infections]
A comprehensive understanding of how Staphylococcus aureus adapts to cause infections in humans can inform development of diagnostic, therapeutic, and preventive approaches. Expression analysis of clinical strain libraries depicts in vitro conditions that differ from those in human infection, but low bacterial burden and the requirement for reverse transcription or nucleic acid amplification complicate such analyses of bacteria causing human infection. We developed methods to evaluate the mRNA transcript signature of S. aureus in pediatric skin and soft tissue infections (SSTI) directly ex vivo. Abscess drainage from 47 he...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Moffitt, K., Cheung, E., Yeung, T., Stamoulis, C., Malley, R. Tags: Bacterial Infections Source Type: research

Spatiotemporal Variations in Growth Rate and Virulence Plasmid Copy Number during Yersinia pseudotuberculosis Infection [Bacterial Infections]
Pathogenic Yersinia spp. depend on the activity of a potent virulence plasmid-encoded ysc/yop type 3 secretion system (T3SS) to colonize hosts and cause disease. It was recently shown that Yersinia pseudotuberculosis upregulates the virulence plasmid copy number (PCN) during infection and that the resulting elevated gene dose of plasmid-encoded T3SS genes is essential for virulence. When and how this novel regulatory mechanism is deployed and regulates the replication of the virulence plasmid during infection is unknown. In the present study, we applied droplet digital PCR (ddPCR) to investigate the dynamics of Y. pseudotu...
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Schneiders, S., Hechard, T., Edgren, T., Avican, K., Fällman, M., Fahlgren, A., Wang, H. Tags: Bacterial Infections Source Type: research

Elevated Extracellular cGMP Produced after Exposure to Enterotoxigenic Escherichia coli Heat-Stable Toxin Induces Epithelial IL-33 Release and Alters Intestinal Immunity [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
In conclusion, our studies indicate that ST modulates epithelial cell physiology and the interplay between the epithelial and immune compartments. (Source: Infection and Immunity)
Source: Infection and Immunity - March 17, 2021 Category: Infectious Diseases Authors: Motyka, N. I., Stewart, S. R., Hollifield, I. E., Kyllo, T. R., Mansfield, J. A., Norton, E. B., Clements, J. D., Bitoun, J. P. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research