Infection and Immunity

Wed, 01/20/2021 - 10:01
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...
Wed, 01/20/2021 - 10:01
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....
Wed, 01/20/2021 - 10:01
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...
Wed, 01/20/2021 - 10:01
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...
Wed, 12/16/2020 - 10:01
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...
Wed, 12/16/2020 - 10:01
A critical facet of mammalian innate immunity involves the hosts’ attempts to sequester and/or limit the availability of key metabolic products from pathogens. For example, nutritional immunity encompasses host approaches to limit the availability of key heavy metal ions such as zinc and iron. Previously, we identified several hundred genes in a multidrug-resistant isolate of Acinetobacter...
Tue, 11/17/2020 - 10:01
Coxiella burnetii is a zoonotic bacterial obligate intracellular parasite and the cause of query (Q) fever. During natural infection of female animals, C. burnetii shows tropism for the placenta and is associated with late-term abortion, at which time the pathogen titer in placental tissue can exceed one billion bacteria per gram. During later stages of pregnancy, placental trophoblasts serve as...
Tue, 11/17/2020 - 10:01
Stimulator of interferon genes (STING) acts as a cytoplasmic signaling hub of innate immunity that is activated by host-derived or bacterially derived cyclic dinucleotides. Listeria monocytogenes is a foodborne, facultative intracellular pathogen that secretes c-di-AMP and activates STING, yet the in vivo role of the STING pathway during bacterial pathogenesis remains unclear. In this study, we...
Tue, 10/20/2020 - 10:01
Upon biofilm formation, production of extracellular matrix components and alteration in physiology and metabolism allows bacteria to build up multicellular communities which can facilitate nutrient acquisition during unfavorable conditions and provide protection toward various forms of environmental stresses to individual cells. Thus, bacterial cells within biofilms become tolerant against...
Tue, 10/20/2020 - 10:01
Porcine circovirus type 2 (PCV2) and Streptococcus suis serotype 2 (SS2) clinical coinfection cases have been frequently detected. The respiratory epithelium plays a crucial role in host defense against a variety of inhaled pathogens. Reactive oxygen species (ROS) are involved in killing of bacteria and host immune response. The aim of this study is to assess whether PCV2 and SS2 coinfection in...
Tue, 10/20/2020 - 10:01
Brucella, the causative agent of brucellosis, is a stealthy intracellular pathogen that is highly pathogenic to a range of mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane and has been implicated in virulence in many bacterial pathogens. However, the roles of the Tat system and related substrates in Brucella remain...
Tue, 10/20/2020 - 10:01
Fingolimod (FTY720), an FDA-approved immunomodulatory drug for treating multiple sclerosis, is an agonist of sphingosine-1-phosphate receptor (S1PR), which has been used as a research tool for inhibiting immune cell trafficking. FTY720 was recently reported to inhibit Chlamydia dissemination. Since genital Chlamydia spreading to the gastrointestinal tract correlated with its pathogenicity in the...
Tue, 10/20/2020 - 10:01
Enterotoxigenic Escherichia coli (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of the class 5 fimbrial family being...
Tue, 10/20/2020 - 10:01
Recent efforts to develop an enterotoxigenic Escherichia coli (ETEC) vaccine have focused on the antigenically conserved tip adhesins of colonization factors. We showed previously that intranasal immunization with dsc19CfaE, a soluble variant of the in cis donor strand-complemented tip adhesin of a colonization factor of the class 5 family (CFA/I) fimbria, is highly immunogenic and protects...
Tue, 10/20/2020 - 10:01
Natural killer (NK) cells are critically involved in the early immune response against various intracellular pathogens, including Coxiella burnetii and Chlamydia psittaci. Chlamydia-infected NK cells functionally mature, induce cellular immunity, and protect themselves by killing the bacteria in secreted granules. Here, we report that infected NK cells do not allow intracellular multiday growth...
Sat, 09/19/2020 - 10:01
Typhoid toxin is a virulence factor of Salmonella enterica serovar Typhi, the causative agent of typhoid fever, and is thought to be responsible for the symptoms of severe disease. This toxin has a unique A2B5 architecture with two active subunits, the ADP ribosyl transferase PltA and the DNase CdtB, linked to a pentameric B subunit, which is alternatively made of PltB or PltC. Here, we describe...
Sat, 09/19/2020 - 10:01
Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate that Brucella abortus, a notorious reproductive...
Sat, 09/19/2020 - 10:01
Reproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with Brucella melitensis is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model. Recently, it was demonstrated...
Sat, 09/19/2020 - 10:01
Successful colonization by enteric pathogens is contingent upon effective interactions with the host and the resident microbiota. These pathogens thus respond to and integrate myriad signals to control virulence. Long-chain fatty acids repress the virulence of the important enteric pathogens Salmonella enterica and Vibrio cholerae by repressing AraC-type transcriptional regulators in...
Sat, 09/19/2020 - 10:01
Biofilm formation by Streptococcus pyogenes (group A streptococcus [GAS]) in model systems mimicking the respiratory tract is poorly documented. Most studies have been conducted on abiotic surfaces, which poorly represent human tissues. We have previously shown that GAS forms mature and antibiotic-resistant biofilms on physiologically relevant epithelial cells. However, the roles of the...
Thu, 08/20/2020 - 10:01
Symptomatic and asymptomatic infection with the diarrheal pathogen enteroaggregative Escherichia coli (EAEC) is associated with growth faltering in children in developing settings. The mechanism of this association is unknown, emphasizing a need for better understanding of the interactions between EAEC and the human gastrointestinal mucosa. In this study, we investigated the role of the...
Thu, 08/20/2020 - 10:01
Enteric pathogens exploit chemical and nutrient signaling to gauge their location within a host and control expression of traits important for infection. Ethanolamine-containing molecules are essential in host physiology and play important roles in intestinal processes. The transcription factor EutR is conserved in the Enterobacteriaceae and is required for ethanolamine sensing and metabolism. In...
Wed, 07/22/2020 - 10:01
Xenophagy targets intracellular pathogens for destruction by the host autophagy pathway. Ubiquitin chains are conjugated to xenophagic targets and recruit multiple autophagy adaptors. The intracellular pathogen Legionella pneumophila resides in a vacuole that is ubiquitinated; however, this pathogen avoids xenophagic detection. Here, the mechanisms by which L. pneumophila can prevent the host...
Wed, 07/22/2020 - 10:01
The intracellular bacterial pathogen Salmonella is able to evade the immune system and persist within the host. In some cases, these persistent infections are asymptomatic for long periods and represent a significant public health hazard because the hosts are potential chronic carriers, yet the mechanisms that control persistence are incompletely understood. Using a mouse model of chronic typhoid...
Tue, 06/23/2020 - 10:01
Chronic bacterial infections are caused by pathogens that persist within their hosts and avoid clearance by the immune system. Treatment and/or detection of such pathogens is difficult, and the resulting pathologies are often deleterious or fatal. There is an urgent need to develop protective vaccines and host-directed therapies that synergize with antibiotics to prevent pathogen persistence and...
Tue, 06/23/2020 - 10:01
The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer that consists of inner leaflet phospholipids and outer leaflet lipopolysaccharides (LPS). The asymmetric character and unique biochemistry of LPS molecules contribute to the OM’s ability to function as a molecular permeability barrier that protects the bacterium against hazards in the environment. Assembly and...
Tue, 06/23/2020 - 10:01
Small noncoding RNAs (ncRNAs) are involved in many important physiological functions in pathogenic microorganisms. Previous studies have identified the presence of noncoding RNAs in the major zoonotic pathogen Campylobacter jejuni; however, few have been functionally characterized to date. CjNC110 is a conserved ncRNA in C. jejuni, located downstream of the luxS gene, which is responsible for the...
Tue, 06/23/2020 - 10:01
Coxiella burnetii is the causative agent of human Q fever, eliciting symptoms that range from acute fever and fatigue to chronic fatal endocarditis. C. burnetii is a Gram-negative intracellular bacterium that replicates within an acidic lysosome-like parasitophorous vacuole (PV) in human macrophages. During intracellular growth, C. burnetii delivers bacterial proteins directly into the host...
Tue, 06/23/2020 - 10:01
Acinetobacter baumannii is a nosocomial pathogen capable of causing a range of diseases, including respiratory and urinary tract infections and bacteremia. Treatment options are limited due to the increasing rates of antibiotic resistance, underscoring the importance of identifying new targets for antimicrobial development. During infection, A. baumannii must acquire nutrients for replication and...
Tue, 06/23/2020 - 10:01
Recent studies have determined that inflammasome signaling plays an important role in driving intestinal epithelial cell (IEC) responses to bacterial infections, such as Salmonella enterica serovar Typhimurium. There are two primary inflammasome pathways, canonical (involving caspase-1) and noncanonical (involving caspase-4 and -5 in humans and caspase-11 in mice). Prior studies identified the...
Thu, 05/21/2020 - 03:36
The zoonotic bacterial pathogen Coxiella burnetii is the causative agent of Q fever, a febrile illness which can cause a serious chronic infection. C. burnetii is a unique intracellular bacterium which replicates within host lysosome-derived vacuoles. The ability of C. burnetii to replicate within this normally hostile compartment is dependent on the activity of the Dot/Icm type 4B secretion...
Thu, 05/21/2020 - 03:36
Clostridioides (formerly Clostridium) difficile is the most common cause of hospital-acquired infection, and advanced age is a risk factor for C. difficile infection. Disruption of the intestinal microbiota and immune responses contribute to host susceptibility and severity of C. difficile infection. However, the specific impact of aging on immune responses during C. difficile infection remains...
Thu, 05/21/2020 - 03:36
Vibrio cholerae is a Gram-negative human pathogen and the causative agent of the life-threatening disease cholera. V. cholerae is a natural inhabitant of marine environments and enters humans through the consumption of contaminated food or water. The ability to transition between aquatic ecosystems and the human host is paramount to the pathogenic success of V. cholerae. The transition between...
Thu, 05/21/2020 - 03:36
Salmonella enterica serovar Typhimurium is an important foodborne pathogen that causes diarrhea. S. Typhimurium elicits inflammatory responses and colonizes the gut lumen by outcompeting the microbiota. Although evidence is accumulating with regard to the underlying mechanism, the infectious stage has not been adequately defined. Peptidoglycan amidases are widely distributed among bacteria and...
Thu, 05/21/2020 - 03:36
Enteroaggregative Escherichia coli (EAEC) is an E. coli pathotype associated with diarrhea and growth faltering. EAEC virulence gene expression is controlled by the autoactivated AraC family transcriptional regulator, AggR. AggR activates transcription of a large number of virulence genes, including Aar, which in turn acts as a negative regulator of AggR itself. Aar has also been shown to affect...
Tue, 04/21/2020 - 03:33
Brucella spp. are facultative intracellular bacteria notorious for their ability to induce a chronic, and often lifelong, infection known as brucellosis. To date, no licensed vaccine exists for prevention of human disease, and mechanisms underlying chronic illness and immune evasion remain elusive. We and others have observed that B cell-deficient mice challenged with Brucella display reduced...
Tue, 04/21/2020 - 03:33
Antimicrobial peptides play an important role in host defense against Vibrio cholerae. Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strains has been reported in recent years, including in the devastating Yemen...
Tue, 03/24/2020 - 03:39
Oral administration is a preferred model for studying infection by bacterial enteropathogens such as Yersinia spp. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration....
Tue, 03/24/2020 - 03:39
Osteoarticular disease is a frequent complication of human brucellosis. Vaccination remains a critical component of brucellosis control, but there are currently no vaccines for use in humans, and no in vitro models for assessing the safety of candidate vaccines in reference to the development of bone lesions currently exist. While the effect of Brucella infection on osteoblasts has been...
Tue, 03/24/2020 - 03:39
Cellular membrane proteins are a critical part of the host defense mechanisms against infection and intracellular survival of Listeria monocytogenes. The complex spatiotemporal regulation of bacterial infection by various membrane proteins has been challenging to study. Here, using mass spectrometry analyses, we depicted the dynamic expression landscape of membrane proteins upon L. monocytogenes...
Tue, 03/24/2020 - 03:39
The complex bacterial populations that constitute the gut microbiota can harbor antibiotic resistance genes (ARGs), including those encoding β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. The prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock....
Tue, 03/24/2020 - 03:39
Nontyphoidal Salmonella species are globally disseminated pathogens and are the predominant cause of gastroenteritis. The pathogenesis of salmonellosis has been extensively studied using in vivo murine models and cell lines, typically challenged with Salmonella enterica serovar Typhimurium. Although S. enterica serovars Enteritidis and Typhimurium are responsible for most of the human infections...
Fri, 02/21/2020 - 03:47
Like many other pathogens, Vibrio cholerae, the causative agent of cholera, can modulate its gene expression to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). We previously reported that the virulence activator AphB in V. cholerae is involved in ROS resistance. In this study, we found that another key virulence regulator...
Fri, 02/21/2020 - 03:47
Multidrug efflux systems belonging to the resistance-nodulation-division (RND) superfamily are ubiquitous in Gram-negative bacteria. RND efflux systems are often associated with multiple antimicrobial resistance and also contribute to the expression of diverse bacterial phenotypes including virulence, as documented in the intestinal pathogen Vibrio cholerae, the causative agent of the severe...
Fri, 02/21/2020 - 03:47
The twin-arginine translocation (Tat) system is involved in not only a wide array of cellular processes but also pathogenesis in many bacterial pathogens; thus, this system is expected to become a novel therapeutic target to treat infections. To the best of our knowledge, involvement of the Tat system has not been reported in the gut infection caused by Citrobacter rodentium. Here, we studied the...
Fri, 02/21/2020 - 03:47
RNA thermometers are cis-acting riboregulators that mediate the posttranscriptional regulation of gene expression in response to environmental temperature. Such regulation is conferred by temperature-responsive structural changes within the RNA thermometer that directly result in differential ribosomal binding to the regulated transcript. The significance of RNA thermometers in controlling...
Fri, 02/21/2020 - 03:47
Salmonella enterica serovar Pullorum is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. In contrast to the strong inflammatory response induced by Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis, S. Pullorum causes systemic infection with little inflammation. The effector proteins secreted by Salmonella...
Fri, 02/21/2020 - 03:47
Modeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells to mechanical forces normally present in the intestine, including luminal flow and serosal blood flow (...
Fri, 02/21/2020 - 03:47
To understand the role of major histocompatibility complex class I (MHC-I) and MHC-II in vaccine-mediated protection against Coxiella burnetii, we evaluated the protective efficacy of a formalin-inactivated C. burnetii Nine Mile phase I vaccine (PIV) in β2-microglobulin-deficient (B2m KO) and MHC-II-deficient (MHC-II KO) mice. Vaccination reduced disease severity in wild-type (WT) and B2m KO...
Fri, 02/21/2020 - 03:47
Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for...

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