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Archives of Microbiology Jan 2021Shigella sonnei is the emerging pathogen globally, as it is the second common infectious species of shigellosis (bloody diarrhoea) in low- and middle-income countries... (Review)
Review
Shigella sonnei is the emerging pathogen globally, as it is the second common infectious species of shigellosis (bloody diarrhoea) in low- and middle-income countries (LMICs) and the leading one in developed world. The multifactorial processes and novel mechanisms have been identified in S. sonnei, that are collectively playing apart a substantial role in increasing its prevalence, while replacing the S. flexneri and other Gram-negative gut pathogens niche occupancy. Recently, studies suggest that due to improvement in sanitation S. sonnei has reduced cross-immunization from Plesiomonas shigelliodes (having same O-antigen as S. sonnei) and also found to outcompete the two major species of Enterobacteriaceae family (Shigella flexneri and Escherichia coli), due to encoding of type VI secretion system (T6SS). This review aimed to highlight S. sonnei as an emerging pathogen in the light of recent research with pondering aspects on its epidemiology, transmission, and pathogenic mechanisms. Additionally, this paper aimed to review S. sonnei disease pattern and related complications, symptoms, and laboratory diagnostic techniques. Furthermore, the available treatment reigns and antibiotic-resistance patterns of S. sonnei are also discussed, as the ciprofloxacin and fluoroquinolone-resistant S. sonnei has already intensified the global spread and burden of antimicrobial resistance. In last, prevention and controlling strategies are briefed to limit and tackle S. sonnei and possible future areas are also explored that needed more research to unravel the hidden mysteries surrounding S. sonnei.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Dysentery, Bacillary; Escherichia coli; Fluoroquinolones; Humans; Shigella flexneri; Shigella sonnei; Type VI Secretion Systems
PubMed: 32929595
DOI: 10.1007/s00203-020-02034-3 -
Microbiology Spectrum Mar 2019is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp.... (Review)
Review
is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp. have also served as model pathogens in the study of bacterial pathogenesis, and has become one of the best-studied pathogens on a molecular, cellular, and tissue level. In the arms race between and the host immune system, has developed highly sophisticated mechanisms to subvert host cell processes in order to promote infection, escape immune detection, and prevent bacterial clearance. Here, we give an overview of pathogenesis while highlighting innovative techniques and methods whose application has significantly advanced our understanding of pathogenesis in recent years.
Topics: Adaptive Immunity; Adhesins, Bacterial; Bacterial Proteins; Cytosol; Dysentery, Bacillary; Epithelial Cells; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immune Evasion; Shigella; Shigella flexneri; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 30953429
DOI: 10.1128/microbiolspec.BAI-0023-2019 -
Cell Jun 2021Gasdermin B (GSDMB) belongs to a large family of pore-forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB...
Gasdermin B (GSDMB) belongs to a large family of pore-forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the IpaH7.8 effector protein secreted by enteroinvasive Shigella flexneri. We show that IpaH7.8 ubiquitinates and targets GSDMB for 26S proteasome destruction. This virulence strategy protects Shigella from the bacteriocidic activity of natural killer cells by suppressing granzyme-A-mediated activation of GSDMB. In contrast to the canonical function of most gasdermin family members, GSDMB does not inhibit Shigella by lysing host cells. Rather, it exhibits direct microbiocidal activity through recognition of phospholipids found on Gram-negative bacterial membranes. These findings place GSDMB as a central executioner of intracellular bacterial killing and reveal a mechanism employed by pathogens to counteract this host defense system.
Topics: Animals; Bacterial Proteins; Biomarkers, Tumor; Cardiolipins; Cell Line; Cell Membrane; Female; Granzymes; Host-Pathogen Interactions; Humans; Killer Cells, Natural; Lipid A; Mice, Inbred C57BL; Mice, Transgenic; Microbial Viability; Neoplasm Proteins; Pore Forming Cytotoxic Proteins; Proteasome Endopeptidase Complex; Protein Binding; Proteolysis; Shigella flexneri; Substrate Specificity; Ubiquitination; Mice
PubMed: 34022140
DOI: 10.1016/j.cell.2021.04.036 -
Cell Host & Microbe Oct 2021The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors...
The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor of GSDMD. Shigella is an enteroinvasive bacterium that causes hemorrhagic gastroenteritis in primates, but not rodents. IpaH7.8 contributes to species specificity by ubiquitinating human, but not mouse, GSDMD and targeting it for proteasomal degradation. Accordingly, infection of human epithelial cells with IpaH7.8-deficient Shigella flexneri results in increased GSDMD-dependent cell death compared with wild type. Consistent with pyroptosis contributing to murine disease resistance, eliminating GSDMD from NLRC4-deficient mice, which are already sensitized to oral infection with Shigella flexneri, leads to further enhanced bacterial replication and increased disease severity. This work highlights a species-specific pathogen arms race focused on maintenance of host cell viability.
Topics: Animals; Bacterial Proteins; Dysentery, Bacillary; Epithelial Cells; Female; Host-Pathogen Interactions; Humans; Mice; Mice, Knockout; Phosphate-Binding Proteins; Pore Forming Cytotoxic Proteins; Proteolysis; Shigella flexneri; Ubiquitin-Protein Ligases
PubMed: 34492225
DOI: 10.1016/j.chom.2021.08.010 -
Frontiers in Cellular and Infection... 2016Autophagy, an intracellular degradation process, is increasingly recognized as having important roles in host defense. Interactions between Shigella flexneri and the... (Review)
Review
Autophagy, an intracellular degradation process, is increasingly recognized as having important roles in host defense. Interactions between Shigella flexneri and the autophagy machinery were first discovered in 2005. Since then, work has shown that multiple autophagy pathways are triggered by S. flexneri, and autophagic responses can have different roles during Shigella infection. Here, we review the interactions between S. flexneri and the autophagy machinery, highlighting that studies using Shigella can reveal the breadth of autophagic responses available to the host.
Topics: Autophagy; Cytoplasm; Dysentery, Bacillary; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammation; Phagocytosis; Shigella flexneri; Vacuoles
PubMed: 26904515
DOI: 10.3389/fcimb.2016.00017 -
IUBMB Life May 2018Innate immunity relies on the effective recognition and elimination of pathogenic microorganisms. This entails sequestration of pathogens into phagosomes that promptly... (Review)
Review
Innate immunity relies on the effective recognition and elimination of pathogenic microorganisms. This entails sequestration of pathogens into phagosomes that promptly acquire microbicidal and degradative properties. This complex series of events, which involve cytoskeletal reorganization, membrane remodeling and the activation of multiple enzymes, is orchestrated by lipid signaling. To overcome this immune response, intracellular pathogens acquired mechanisms to subvert phosphoinositide-mediated signaling and use host lipids, notably cholesterol, as nutrients. We present brief overviews of the role of phosphoinositides in phagosome formation and maturation as well as of cholesterol handling by host cells, and selected Salmonella, Shigella, Chlamydia and Mycobacterium tuberculosis to exemplify the mechanisms whereby intracellular pathogens co-opt lipid metabolism in host cells. © 2018 IUBMB Life, 70(5):384-392, 2018.
Topics: Animals; Bacterial Infections; Chlamydia trachomatis; Cholesterol; Host-Pathogen Interactions; Humans; Immunity, Innate; Lipid Droplets; Lipid Metabolism; Macrophages; Mycobacterium tuberculosis; Phagosomes; Phosphatidylinositols; Salmonella enterica; Shigella flexneri; Signal Transduction
PubMed: 29573124
DOI: 10.1002/iub.1737 -
Journal of Bacteriology Nov 2021Shigella flexneri is an intracellular human pathogen that invades colonic cells and causes bloody diarrhea. S. flexneri evolved from commensal Escherichia coli, and...
Shigella flexneri is an intracellular human pathogen that invades colonic cells and causes bloody diarrhea. S. flexneri evolved from commensal Escherichia coli, and genome comparisons reveal that S. flexneri has lost approximately 20% of its genes through the process of pathoadaptation, including a disproportionate number of genes associated with the turnover of the nucleotide-based second messenger cyclic di-GMP (c-di-GMP); however, the remaining c-di-GMP turnover enzymes are highly conserved. c-di-GMP regulates many behavioral changes in other bacteria in response to changing environmental conditions, including biofilm formation, but this signaling system has not been examined in S. flexneri. In this study, we expressed VCA0956, a constitutively active c-di-GMP synthesizing diguanylate cyclase (DGC) from Vibrio cholerae, in S. flexneri to determine if virulence phenotypes were regulated by c-di-GMP. We found that expressing VCA0956 in S. flexneri increased c-di-GMP levels, and this corresponds with increased biofilm formation and reduced acid resistance, host cell invasion, and plaque size. We examined the impact of VCA0956 expression on the S. flexneri transcriptome and found that genes related to acid resistance were repressed, and this corresponded with decreased survival to acid shock. We also found that individual S. flexneri DGC mutants exhibit reduced biofilm formation and reduced host cell invasion and plaque size, as well as increased resistance to acid shock. This study highlights the importance of c-di-GMP signaling in regulating S. flexneri virulence phenotypes. The intracellular human pathogen causes dysentery, resulting in as many as one million deaths per year. Currently, there is no approved vaccine for the prevention of shigellosis, and the incidence of antimicrobial resistance among species is on the rise. Here, we explored how the widely conserved c-di-GMP bacterial signaling system alters behaviors associated with pathogenesis. We found that expressing or removing enzymes associated with c-di-GMP synthesis results in changes in 's ability to form biofilms, invade host cells, form lesions in host cell monolayers, and resist acid stress.
Topics: Aquaculture; Cyclic GMP; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Genome, Bacterial; Mutation; Phosphorus-Oxygen Lyases; Shigella flexneri; Transcriptome; Virulence
PubMed: 34543105
DOI: 10.1128/JB.00242-21 -
The Indian Journal of Medical Research May 2016Shigellosis is one of the major causes of diarrhoea in India. The accurate estimates of morbidity and mortality due to shigellosis are lacking, though it is endemic in... (Review)
Review
Shigellosis is one of the major causes of diarrhoea in India. The accurate estimates of morbidity and mortality due to shigellosis are lacking, though it is endemic in the country and has been reported to cause many outbreaks. The limited information available indicates Shigella to be an important food- borne pathogen in India. S. flexneri is the most common species, S. sonnei and non-agglutinable Shigellae seem to be steadily surfacing, while S. dysenteriae has temporarily disappeared from the northern and eastern regions. Antibiotic-resistant strains of different Shigella species and serotypes have emerged all over the world. Especially important is the global emergence of multidrug resistant Shigellae, notably the increasing resistance to third generation cephalosporins and fluoroquinolones, and also azithromycin. This calls for a continuous and strong surveillance of antibiotic resistance across the country for periodic updation of the local antibiograms. The prevention of shigellosis is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country. Public health measures like provision of safe water and adequate sanitation are of immense importance to reduce the burden of shigellosis, however, the provision of resources to develop such an infrastructure in India is a complex issue and will take time to resolve. Thus, the scientific thrust should be focused towards development of a safe and affordable multivalent vaccine. this review is focused upon the epidemiology, disease burden and the therapeutic challenges of shigellosis in Indian perspective.
Topics: Anti-Bacterial Agents; Diarrhea; Disease Outbreaks; Dysentery, Bacillary; Fluoroquinolones; Humans; India; Microbial Sensitivity Tests; Shigella flexneri
PubMed: 27487999
DOI: 10.4103/0971-5916.187104 -
Emerging Infectious Diseases Jun 2022Annually, Shigella spp. cause ≈188 million cases of diarrheal disease globally, including 500,000 cases in the United States; rates of antimicrobial resistance are... (Review)
Review
Annually, Shigella spp. cause ≈188 million cases of diarrheal disease globally, including 500,000 cases in the United States; rates of antimicrobial resistance are increasing. To determine antimicrobial resistance and risk factors in San Diego, California, USA, we retrospectively reviewed cases of diarrheal disease caused by Shigella flexneri and S. sonnei diagnosed during 2017-2020. Of 128 evaluable cases, S. flexneri was slightly more common than S. sonnei; most cases were in persons who were gay or bisexual cisgender men, were living with HIV, were unhoused, or used methamphetamines. Overall, rates of resistance to azithromycin, fluoroquinolones, ampicillin, and trimethoprim/sulfamethoxazole (TMP/SMX) were comparable to the most recent national data reported from the Centers for Disease Control and Prevention; 55% of isolates were resistant to azithromycin, 23% to fluoroquinolones, 70% to ampicillin, and 83% to TMP/SMX. The rates that we found for TMP/SMX were slightly higher than those in national data.
Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; California; Diarrhea; Drug Resistance, Bacterial; Dysentery, Bacillary; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Retrospective Studies; Shigella; Shigella sonnei; Trimethoprim, Sulfamethoxazole Drug Combination; United States
PubMed: 35608550
DOI: 10.3201/eid2806.220131 -
Frontiers in Cellular and Infection... 2016Shigella is a pathovar of Escherichia coli comprising four groups, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, and Shigella boydii, each of them, with the... (Review)
Review
Shigella is a pathovar of Escherichia coli comprising four groups, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, and Shigella boydii, each of them, with the exception of S.sonnei, comprising several serotypes. Shigella accounts for the majority of dysentery causing infections occurring world-wide each year. Recent advancements in the Shigella field have led to a better understanding of the molecular mechanisms underlying host epithelial cell invasion and immune cell function manipulation, mainly using S. flexneri as a model. Host-cell invasion is the final step of the infection process, as Shigella's virulence strategy relies also on its ability to survive hostile conditions during its journey through the gastro-intestinal tract, to compete with the host microbiota and to cross the intestinal mucus layer. Hence, the diversity of the virulence strategies among the different Shigella species has not yet been deeply investigated, which might be an important step to understand the epidemiological spreading of Shigella species worldwide and a key aspect for the validation of novel vaccine candidates. The recent development of high-throughput screening and sequencing methods will facilitate these complex comparison studies. In this review we discuss several of the major avenues that the Shigella research field has taken over the past few years and hopefully gain some insights into the questions that remain surrounding this important human pathogen.
Topics: Dysentery, Bacillary; Epithelial Cells; Geography; Host-Pathogen Interactions; Humans; Shigella boydii; Shigella dysenteriae; Shigella flexneri; Shigella sonnei
PubMed: 27148494
DOI: 10.3389/fcimb.2016.00045