Vibrio parahaemolyticus
(Vp) is an aquatic Gram-negative bacterium that may infect humans and cause gastroenteritis and wound infections. The first pandemic of Vp associated infection was caused by ...the serovar O3:K6 and epidemics caused by the other serovars are increasingly reported. The two major virulence factors, thermostable direct hemolysin (TDH) and/or TDH-related hemolysin (TRH), are associated with hemolysis and cytotoxicity. Vp strains lacking
tdh
and/or
trh
are avirulent and able to colonize in the human gut and cause infection using other unknown factors. This pathogen is well adapted to survive in the environment and human host using several genetic mechanisms. The presence of prophages in Vp contributes to the emergence of pathogenic strains from the marine environment. Vp has two putative type-III and type-VI secretion systems (T3SS and T6SS, respectively) located on both the chromosomes. T3SS play a crucial role during the infection process by causing cytotoxicity and enterotoxicity. T6SS contribute to adhesion, virulence associated with interbacterial competition in the gut milieu. Due to differential expression, type III secretion system 2 (encoded on chromosome-2, T3SS2) and other genes are activated and transcribed by interaction with bile salts within the host. Chromosome-1 encoded T6SS1 has been predominantly identified in clinical isolates. Acquisition of genomic islands by horizontal gene transfer provides enhanced tolerance of Vp toward several antibiotics and heavy metals. Vp consists of evolutionarily conserved targets of GTPases and kinases. Expression of these genes is responsible for the survival of Vp in the host and biochemical changes during its survival. Advanced genomic analysis has revealed that various genes are encoded in Vp pathogenicity island that control and expression of virulence in the host. In the environment, the biofilm gene expression has been positively correlated to tolerance toward aerobic, anaerobic, and micro-aerobic conditions. The genetic similarity analysis of toxin/antitoxin systems of
Escherichia coli
with VP genome has shown a function that could induce a viable non-culturable state by preventing cell division. A better interpretation of the Vp virulence and other mechanisms that support its environmental fitness are important for diagnosis, treatment, prevention and spread of infections. This review identifies some of the common regulatory pathways of Vp in response to different stresses that influence its survival, gut colonization and virulence.
Triple negative breast cancer (TNBC) is classically treated with combination chemotherapies. Although, initially responsive to chemotherapies, TNBC patients frequently develop drug-resistant, ...metastatic disease. Chemotherapy resistance can develop through many mechanisms, including induction of a transient growth-arrested state, known as the therapy-induced senescence (TIS). In this paper, we will focus on chemoresistance in TNBC due to TIS. One of the key characteristics of senescent cells is a complex secretory phenotype, known as the senescence-associated secretory proteome (SASP), which by prompting immune-mediated clearance of senescent cells maintains tissue homeostasis and suppresses tumorigenesis. However, in cancer, particularly with TIS, senescent cells themselves as well as SASP promote cellular reprograming into a stem-like state responsible for the emergence of drug-resistant, aggressive clones. In addition to chemotherapies, outcomes of recently approved immune and DNA damage-response (DDR)-directed therapies are also affected by TIS, implying that this a common strategy used by cancer cells for evading treatment. Although there has been an explosion of scientific research for manipulating TIS for prevention of drug resistance, much of it is still at the pre-clinical stage. From an evolutionary perspective, cancer is driven by natural selection, wherein the fittest tumor cells survive and proliferate while the tumor microenvironment influences tumor cell fitness. As TIS seems to be preferred for increasing the fitness of drug-challenged cancer cells, we will propose a few tactics to control it by using the principles of evolutionary biology. We hope that with appropriate therapeutic intervention, this detrimental cellular fate could be diverted in favor of TNBC patients.
The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, ...across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa.
(
) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body.
acquires antibiotic resistance ...determinants easily and can thrive on both biotic and abiotic surfaces. Different resistance mechanisms or determinants, both transmissible and non-transmissible, have aided in this victory over antibiotics. In addition, the propensity to form biofilms (communities of organism attached to a surface) allows the organism to persist in hospitals on various medical surfaces (cardiac valves, artificial joints, catheters, endotracheal tubes, and ventilators) and also evade antibiotics simply by shielding the bacteria and increasing its ability to acquire foreign genetic material through lateral gene transfer. The biofilm formation rate in
is higher than in other species. Recent research has shown how
biofilm-forming capacity exerts its effect on resistance phenotypes, development of resistome, and dissemination of resistance genes within biofilms by conjugation or transformation, thereby making biofilm a hotspot for genetic exchange. Various genes control the formation of
biofilms and a beneficial relationship between biofilm formation and "antimicrobial resistance" (AMR) exists in the organism. This review discusses these various attributes of the organism that act independently or synergistically to cause hospital infections. Evolution of AMR in
, resistance mechanisms including both transmissible (hydrolyzing enzymes) and non-transmissible (efflux pumps and chromosomal mutations) are presented. Intrinsic factors biofilm-associated protein, outer membrane protein A, chaperon-usher pilus, iron uptake mechanism, poly-β-(1, 6)-N-acetyl glucosamine, BfmS/BfmR two-component system, PER-1, quorum sensing involved in biofilm production, extrinsic factors (surface property, growth temperature, growth medium) associated with the process, the impact of biofilms on high antimicrobial tolerance and regulation of the process, gene transfer within the biofilm, are elaborated. The infections associated with colonization of
on medical devices are discussed. Each important device-related infection is dealt with and both adult and pediatric studies are separately mentioned. Furthermore, the strategies of preventing
biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.
It has been well known that Vibrio cholerae inhabit in environmental water. As many patients infected with cholera toxin-producing V. cholerae O1 (toxigenic V. cholerae O1) emerge in Kolkata, India, ...it has been thought that toxigenic V. cholerae O1 is easily detected in environmental water in Kolkata. However, we could not isolate toxigenic V. cholerae O1 from environmental water in Kolkata, though NAG Vibrio (generic name of V. cholerae non-O1/non-O139) is constantly detected. To clear the reason for the non-isolation of toxigenic V. cholerae O1, we examined the viability of V. cholera O1 and NAG Vibrios in the artificial low ionic strength aquatic solution. We found that the viability of toxigenic V. cholerae O1 in the solution is low, but that of NAG Vibrios is high. Subsequently, we examined the viability of NAG Vibrios possessing cholera toxin gene (ctx) in the same condition and found that the viability of these NAG Vibrios is low. These results indicate that the existence of ctx in V. cholerae affects the viability of V. cholerae in the aquatic solution used in this experiment. We thought that there was closely relation between the low viability of toxigenic V. cholerae O1 in the artificial low ionic strength aquatic solution and the low frequency of isolation of the strain from environmental water.
The diagnostic assays currently used to detect Shigella spp. (Shigella) and enterotoxigenic Escherichia coli (ETEC) are complex or elaborate which make them difficult to apply in resource poor ...settings where these diseases are endemic. The simple and rapid nucleic acid amplification-based assay "Rapid LAMP-based Diagnostic Test (RLDT)" was evaluated to detect Shigella spp (Shigella) and enterotoxigenic Escherichia coli (ETEC) and determine the epidemiology of these pathogens in Kolkata, India. Stool samples (n = 405) from children under five years old with diarrhea seeking care at the hospitals were tested, and 85(21%) and 68(17%) by RLDT, 91(23%) and 58(14%) by quantitative PCR (qPCR) and 35(9%) and 15(4%) by culture, were positive for Shigella and ETEC, respectively. The RLDT showed almost perfect agreement with qPCR, Kappa 0.96 and 0.89; sensitivity 93% and 98%; specificity 100% and 97% for Shigella and ETEC, respectively. While RLDT detected additional 12% Shigella and 13% ETEC than culture, all culture positives for Shigella and ETEC except one each were also positive by the RLDT, sensitivity 97% and 93% respectively. RLDT is a simple, sensitive, and rapid assay that could be implemented with minimum training in the endemic regions to strengthen the disease surveillance system and rapid outbreak detection.
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common serovar associated with non-typhoidal salmonellosis globally. However, there is insufficient data on molecular characterization of ...S. Typhimurium isolates from India. This study was undertaken to determine the antimicrobial resistance (AMR), plasmid, virulence profiles and molecular subtypes of S. Typhimurium Indian isolates (n = 70) of clinical and environmental origin isolated during 2010-2017. Antimicrobial susceptibility and minimum inhibitory concentrations were determined by disc diffusion and E-test methods respectively. Plasmid extraction was done following standard protocol. AMR genes, virulence genes and plasmid incompatibility types were detected by PCR; Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular subtyping. Majority (57%) of the study isolates was pan susceptible; five AMR profiles were observed among the resistant (43%) isolates. AMR was significantly (p = 0.004) associated with extra-intestinal isolates than intestinal isolates.The class 1 integron and plasmid-mediated quinolone resistance genes (qnrB1, qnrS1) in the resistant isolates were transferable by conjugation. Plasmids (≥1) ranging from 1.9 to 254kb size and of IncFIIS and/or FIB type were found in most isolates. A total of 39 pulsotypes by PFGE and four sequence types by MLST like ST36 (55.7%), ST19 (32.9%), ST313 (10%) and ST213 (1.4%) were observed. ST36 and ST19 were found circulating in both clinical and environmental host, while ST313 isolates had an exclusive clinical origin. All ST19 isolates (100%) were drug-resistant, while isolates belonging to ST313 (100%), ST213 (100%) and ST36 (82%) were pan susceptible. The virulence plasmid (VP) genes (spvB- spvC) were present in all genotypes except ST36. The VP was significantly (p<0.001) associated with extra-intestinal than intestinal isolates. Some environmental and clinical isolates were clonal indicating their zoonotic transmission. Knowledge on the molecular subtypes and AMR profiles of locally prevalent Salmonella serotypes is important for effective control of spread of resistant organisms. The MLST of S. Typhimurium isolates and its association with AMR, virulence profiles was not reported earlier from India.
The primary aim of this study was to investigate the occurrence, characteristics, and antimicrobial resistance patterns of various Shigella serogroups isolated from patients with acute diarrhea of ...the Infectious Diseases Hospital in Kolkata from 2011-2019.
During the study period, Shigella isolates were tested for their serogroups, antibiotic resistance pattern and virulence gene profiles. A total of 5.8% of Shigella spp. were isolated, among which S. flexneri (76.1%) was the highest, followed by S. sonnei (18.7%), S. boydii (3.4%), and S. dysenteriae (1.8%). Antimicrobial resistance against nalidixic acid was higher in almost all the Shigella isolates, while the resistance to β-lactamases, fluoroquinolones, tetracycline, and chloramphenicol diverged. The occurrence of multidrug resistance was found to be linked with various genes encoding drug-resistance, multiple mutations in the topoisomerase genes, and mobile genetic elements. All the isolates were positive for the invasion plasmid antigen H gene (ipaH). Dendrogram analysis of the plasmid and pulsed-field electrophoresis (PFGE) profiles revealed 70-80% clonal similarity among each Shigella serotype.
This comprehensive long-term surveillance report highlights the clonal diversity of clinical Shigella strains circulating in Kolkata, India, and shows alarming resistance trends towards recommended antibiotics. The elucidation of this study's outcome is helpful not only in identifying emerging antimicrobial resistance patterns of Shigella spp. but also in developing treatment guidelines appropriate for this region.
Non‐O1/non‐O139 nontoxigenic Vibrio cholerae associated with cholera‐like diarrhea has been reported in Kolkata, India. However, the property involved in the pathogenicity of these strains has ...remained unclear. The character of 25 non‐O1/non‐O139 nontoxigenic V. cholerae isolated during 8 years from 2007 to 2014 in Kolkata was examined. Determination of the serogroup showed that the serogroups O6, O10, O35, O36, O39, and O70 were represented by two strains in each serogroup, and the remaining isolates belonged to different serogroups. To clarify the character of antibiotic resistance of these isolates, an antibiotic resistance test and the gene analysis were performed. According to antimicrobial drug susceptibility testing, 13 strains were classified as drug resistant. Among them, 10 strains were quinolone resistant and 6 of the 13 strains were resistant to more than three antibiotics. To define the genetic background of the antibiotic character of these strains, whole‐genome sequences of these strains were determined. From the analysis of these sequences, it becomes clear that all quinolone resistance isolates have mutations in quinolone resistance‐determining regions. Further research on the genome sequence showed that four strains possess Class 1 integrons in their genomes, and that three of the four integrons are found to be located in their genomic islands. These genomic islands are novel types. This indicates that various integrons containing drug resistance genes are spreading among V. cholerae non‐O1/non‐O139 strains through the action of newly generated genomic islands.
Acute diarrheal disease is a major health problem, and the second most common cause of death in children under 5 years of age. Conventional diagnostic methods are laborious, time consuming, and ...occasionally inaccurate. We used SYBR-Green real-time PCR for the detection of 10 uncommon bacterial pathogens using fecal specimens from acute diarrheal patients. In the SYBR-Green real-time PCR assay, the products formed were identified based on a melting point temperature curve analysis, and the assay was validated with the respective reference strain. In a retrospective study, we tested 1,184 stool specimens previously examined using conventional culture methods. Enterotoxigenic Bacteriodes fragilis was detected in 6.7% of the samples followed by enterotoxigenic Bacillus cereus (5.1%), Clostridium perfringens (3.9%), and Aeromonas hydrophila (3.8%). In the prospective study, A. hydrophila, Staphylococcus aureus, and C. perfringens were predominantly detected in 11 > 5 years of age, using real-time PCR. The real-time PCR assay is comprehensive, rapid, accurate, and well suited for surveillance or diagnostic purposes to detect uncommon bacterial pathogens, and should be useful in initiating appropriate care and thereby reducing patient risk.
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