-
Virulence Dec 2023spp. are the causative agent of shigellosis (or bacillary dysentery), a diarrhoeal disease characterized for the bacterial invasion of gut epithelial cells. Among the 4... (Review)
Review
spp. are the causative agent of shigellosis (or bacillary dysentery), a diarrhoeal disease characterized for the bacterial invasion of gut epithelial cells. Among the 4 species included in the genus, is principally responsible for the disease in the developing world while is the main causative agent in high-income countries. Remarkably, as more countries improve their socioeconomic conditions, we observe an increase in the relative prevalence of . To date, the reasons behind this change in aetiology depending on economic growth are not understood. has been widely used as a model to study the pathogenesis of the genus, but as more research data are collected, important discrepancies with have come to light. In comparison to can be differentiated in numerous aspects; it presents a characteristic O-antigen identical to that of one serogroup of the environmental bacterium , a group 4 capsule, antibacterial mechanisms to outcompete and displace gut commensal bacteria, and a poorer adaptation to an intracellular lifestyle. In addition, the World Health Organization (WHO) have recognized the significant threat posed by antibiotic-resistant strains of , demanding new approaches. This review gathers knowledge on what is known about within the context of other spp. and aims to open the door for future research on understanding the increasing spread of this pathogen.
Topics: Humans; Shigella sonnei; Virulence; Prevalence; Anti-Bacterial Agents; Cell Differentiation; Dysentery, Bacillary
PubMed: 37994877
DOI: 10.1080/21505594.2023.2280838 -
Applied and Environmental Microbiology Dec 2023is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant strains has caused an emergent need for the development of...
is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant strains has caused an emergent need for the development of new antimicrobial agents against this pathogenic bacterium. In this study, we demonstrate that Stattic employs two antibacterial mechanisms against . It exerted both anti-virulence activity and bactericidal activity against , suggesting that it shows advantages over traditional antibiotics. Moreover, Stattic showed excellent synergistic effects with kanamycin, ampicillin, chloramphenicol, and gentamicin against . Our findings suggest that Stattic has promising potential for development as a new antibiotic or as an adjuvant to antibiotics for infections caused by .
Topics: Humans; Shigella sonnei; Anti-Bacterial Agents; Dysentery, Bacillary; Ampicillin; Microbial Sensitivity Tests; Shigella
PubMed: 38032177
DOI: 10.1128/aem.01074-23 -
Cureus Jan 2024Due to their propensity for causing diarrheal illnesses and their rising susceptibility to antimicrobials, Shigella infections constitute a serious threat to global... (Review)
Review
Due to their propensity for causing diarrheal illnesses and their rising susceptibility to antimicrobials, Shigella infections constitute a serious threat to global public health. This extensive study explores the frequency, antibiotic resistance, genetic evolution, and effects of Shigella infections on vulnerable groups. The research covers a wide range of geographical areas and sheds information on how the prevalence of Shigella species is evolving. Shigella strain antimicrobial resistance patterns are thoroughly examined. Multidrug resistance (MDR) has been found to often occur in investigations, especially when older antimicrobials are used. The improper use of antibiotics in China is blamed for the quick emergence of resistance, and variations in resistance rates have been seen across different geographical areas. Shigella strains' genetic makeup can be used to identify emerging trends and horizontal gene transfer's acquisition of resistance genes. Notably, S. sonnei exhibits the capacity to obtain resistance genes from nearby bacteria, increasing its capacity for infection. The study also emphasizes the difficulties in accurately serotyping Shigella strains due to inconsistencies between molecular and conventional serology. These results highlight the necessity of reliable diagnostic methods for monitoring Shigella infections. In conclusion, this study emphasizes how dynamic Shigella infections are, with varying patterns of occurrence, changing resistance landscapes, and genetic adaptability. In addition to tackling the rising problem of antibiotic resistance in Shigella infections, these findings are essential for guiding efforts for disease surveillance, prevention, and treatment.
PubMed: 38435906
DOI: 10.7759/cureus.53276 -
Microbiology (Reading, England) Feb 2024The mammalian colon is one of the most densely populated habitats currently recognised, with 10-10 commensal bacteria per gram of colonic contents. Enteric pathogens...
The mammalian colon is one of the most densely populated habitats currently recognised, with 10-10 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are species which cause approximately 125 million infections annually, of which over 90 % are caused by and was previously reported to use a Type VI Secretion System (T6SS) to outcompete and in and experiments. strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of . We reveal that whilst the T6SS operon is present in there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our assays was due to colicin activity. We show that no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from abrogated anti-bacterial activity of . We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by within the gastrointestinal environment.
Topics: Animals; Shigella sonnei; Colicins; Escherichia coli; Bacteria; Gastrointestinal Contents; Mammals
PubMed: 38376387
DOI: 10.1099/mic.0.001434 -
Frontiers in Molecular Biosciences 2023Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5 years in low- and middle-income countries, and increasing number of...
Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5 years in low- and middle-income countries, and increasing number of reports of cases associated to anti-microbial resistance. No vaccines against are still licensed, but different candidates based on the O-antigen portion of lipopolysaccharides are in clinic. Generalized Modules for Membrane Antigens (GMMA) have been proposed as an alternative delivery system for the O-antigen, and a 4-component vaccine candidate (altSonflex1-2-3), containing GMMA from and 1b, 2a and 3a is being tested in a phase 1/2 clinical trial, with the aim to elicit broad protection against the most prevalent serotypes. Here, the 4-component GMMA vaccine candidate has been compared to a more traditional glycoconjugate formulation for the ability to induce functional antibodies in mice and rabbits. In mice, in the absence of Alhydrogel, GMMA induce higher IgG antibodies than glycoconjugates and stronger bactericidal titers against all serotypes. In the presence of Alhydrogel, GMMA induce O-antigen specific IgG levels similar to traditional glycoconjugates, but with a broader range of IgG subclasses, resulting in stronger bactericidal activity. In rabbits, GMMA elicit higher functional antibodies than glycoconjugates against , and similar responses to 1b, 2a and 3a, independently from the presence of Alhydrogel. Different O-antigen based vaccines against are now in clinical stage and it will be of particular interest to understand how the preclinical findings in the different animal models translate in humans.
PubMed: 38046812
DOI: 10.3389/fmolb.2023.1284515 -
Microbiology Spectrum Jun 2023Many bacteria use small molecules, such as quorum sensing (QS) signals, to perform intraspecies signaling and interspecies or interkingdom communication. Previous...
Many bacteria use small molecules, such as quorum sensing (QS) signals, to perform intraspecies signaling and interspecies or interkingdom communication. Previous studies demonstrated that some bacteria regulate their physiology and pathogenicity by employing 4-hydroxybenzoic acid (4-HBA). Here, we report that 4-HBA controls biological functions, virulence, and anthranilic acid production in Shigella sonnei. The biosynthesis of 4-HBA is performed by UbiC (SSON_4219), which is a chorismate pyruvate-lyase that catalyzes the conversion of chorismate to 4-HBA. Deletion of caused S. sonnei to exhibit impaired phenotypes, including impaired biofilm formation, extracellular polysaccharide (EPS) production, and virulence. In addition, we found that 4-HBA controls the physiology and virulence of S. sonnei through the response regulator AaeR (SSON_3385), which contains a helix-turn-helix (HTH) domain and a LysR substrate-binding (LysR_substrate) domain. The same biological functions are controlled by AaeR and the 4-HBA signal, and 4-HBA-deficient mutant phenotypes were rescued by in expression of AaeR. We found that 4-HBA binds to AaeR and then enhances the binding of AaeR to the promoter DNA regions in target genes. Moreover, we revealed that 4-HBA from S. sonnei reduces the competitive fitness of Candida albicans by interfering with morphological transition. Together, our results suggested that the 4-HBA signaling system plays crucial roles in bacterial physiology and interkingdom communication. Shigella sonnei is an important pathogen in human intestines. Following previous findings that some bacteria employ 4-HBA as a QS signal to regulate biological functions, we demonstrate that 4-HBA controls the physiology and virulence of S. sonnei. This study is significant because it identifies both the signal synthase UbiC and receptor AaeR and unveils the signaling pathway of 4-HBA in S. sonnei. In addition, this study also supports the important role of 4-HBA in microbial cross talk, as 4-HBA strongly inhibits hyphal formation by Candida albicans. Together, our findings describe the dual roles of 4-HBA in both intraspecies signaling and interkingdom communication.
Topics: Humans; Virulence; Shigella sonnei; Bacteria; Signal Transduction
PubMed: 37036340
DOI: 10.1128/spectrum.04835-22 -
Gut Microbes Dec 2023spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of entire life cycle and the...
spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of entire life cycle and the evaluation of vaccine candidates' protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (, 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased penetration into the colon epithelium layer in a Gulo mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both infection strategies and immune responses to infection.
Topics: Guinea Pigs; Humans; Animals; Rabbits; Mice; Dysentery, Bacillary; Gastrointestinal Microbiome; Shigella; Disease Models, Animal; Shigella flexneri; Ascorbic Acid; Mammals
PubMed: 37876025
DOI: 10.1080/19490976.2023.2271597 -
Emerging Infectious Diseases Aug 2023We report extensively drug-resistant (XDR) Shigella sonnei infection in an immunocompromised patient in Texas, USA. Matrix-assisted laser desorption/ionization...
We report extensively drug-resistant (XDR) Shigella sonnei infection in an immunocompromised patient in Texas, USA. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify XDR Shigella, but whole-genome sequencing accurately characterized the strain. First-line antimicrobials are not effective against emerging XDR Shigella. Fosfomycin, carbapenems, and tigecycline are potential alternatives.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Dysentery, Bacillary; Microbial Sensitivity Tests; Shigella; Shigella sonnei; United States
PubMed: 37486233
DOI: 10.3201/eid2908.230411 -
Gene May 2024Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its...
BACKGROUND
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent.
AIM
To explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein.
METHODS
Clinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control.
RESULTS
Compared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics.
CONCLUSION
Enteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.
Topics: Humans; RNA, Ribosomal, 16S; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Microbiota; Feces; Dysbiosis
PubMed: 38367851
DOI: 10.1016/j.gene.2024.148257 -
MSphere Aug 2023The artificial invasin complex (Invaplex) vaccine is a subunit approach that effectively induces robust immunogenicity directed to serotype-specific lipopolysaccharide...
The artificial invasin complex (Invaplex) vaccine is a subunit approach that effectively induces robust immunogenicity directed to serotype-specific lipopolysaccharide and the broadly conserved IpaB and IpaC proteins. One advantage of the vaccine approach is the ability to adjust the constituents to address suboptimal immunogenicity and to change the serotype targeted by the vaccine. As the vaccine moves through the product development pipeline, substantial modifications have been made to address manufacturing feasibility, acceptability to regulatory authorities, and developing immunogenic and effective products for an expanded list of serotypes. Modifications of the recombinant clones used to express affinity tag-free proteins using well-established purification methods, changes to detergents utilized in the assembly process, and and evaluation of different Invaplex formulations have led to the establishment of a scalable, reproducible manufacturing process and enhanced immunogenicity of Invaplex products designed to protect against four of the most predominant serotypes responsible for global morbidity and mortality. These adjustments and improvements provide the pathway for the manufacture and clinical testing of a multivalent Invaplex vaccine. IMPORTANCE species are a major global health concern that cause severe diarrhea and dysentery in children and travelers to endemic areas of the world. Despite significant advancements in access to clean water, the increases in antimicrobial resistance and the risk of post-infection sequelae, including cognitive and physical stunting in children, highlight the urgent need for an efficacious vaccine. One promising vaccine approach, artificial Invaplex, delivers key antigens recognized by the immune system during infection, which results in increased resistance to re-infection. The work presented here describes novel modifications to a previously described vaccine approach resulting in improved methods for manufacturing and regulatory approvals, expansion of the breadth of coverage to all major serotypes, and an increase in the potency of artificial Invaplex.
Topics: Child; Humans; Shigella flexneri; Shigella Vaccines; Shigella; Lipopolysaccharides; Vaccines
PubMed: 37389412
DOI: 10.1128/msphere.00073-23