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Acinetobacter baumannii ( A. baumannii ) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body. A. baumannii 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 A. baumannii is higher than in other species. Recent research has shown how A. baumannii 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 A. baumannii 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 A. baumannii , 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 A. baumannii 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 A. baumannii biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.

•Cholera is a major public health problem in several Asian and African countries.•Effective management is crucial in controlling the epidemics of cholera.•RDTs are useful in the identification of Vibrio cholerae O1/O139.•At the point-of-care facilities, RDTs help in making appropriate decisions.•This article updates current knowledge on various RDTs and their effective use. Cholera caused by the toxigenic Vibrio cholerae is still a major public health problem in many countries. This disease is mainly due to poor sanitation, hygiene and consumption of unsafe water. Several recent epidemics of cholera showed its increasing intensity, duration and severity of the illness. This indicates an urgent need for effective management and preventive measures in controlling the outbreaks and epidemics. In preventing and spread of epidemic cholera, rapid diagnostic tests (RDTs) are useful in screening suspected stool specimens, water/food samples. Several RDTs developed recently are considered as investigative tools in confirming cholera cases, as the culture techniques are difficult to establish and/or maintain. The usefulness of RDTs will be more at the point-of-care facilities as it helps to make appropriate decisions in the management of outbreaks or epidemiological surveillance by the public health authorities. Apart from RDTs, several other tests are available for the direct detection of either V. cholerae or its cholera toxin. Viable but non-culturable (VBNC) state of V. cholerae poses a great challenge in developing RDTs. The aim of this article is to provide an overview of current knowledge about RDT and other techniques with reference to their status and future potentials in detecting cholera/V. cholerae.

Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)(+ve) and cag(-ve) Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

Background Cholera, an acute diarrheal disease is a major public health problem in many developing countries. Several rapid diagnostic tests (RDT) are available for the detection of cholera, but their efficacies are not compared in an endemic setting. In this study, we have compared the specificity and sensitivity of three RDT kits for the detection of Vibrio cholerae O1 and compared their efficiency with culture and polymerase chain reaction (PCR) methods. Methods Five hundred six diarrheal stool samples collected from patients from two different hospitals in Kolkata, India were tested using SD Bioline Cholera, SMART-II Cholera O1 and Crystal-VC RDT kits. All the stool samples were screened for the presence of V. cholerae by direct and enrichment culture methods. Stool DNA-based PCR assay was made to target the cholera toxin (ctxAB) and O1 somatic antigen (rfb) encoding genes. Statistical evaluation of the RDTs has been made using STATA software with stool culture and PCR results as the gold standards. The Bayesian latent class model (LCM) was used to evaluate the diagnostic tests in the absence of the gold standard. Results Involving culture technique as gold standard, the sensitivity and specificity of the cholera RDT kits in the direct testing of stools was highest with SAMRT-II (86.1%) and SD-Cholera (94.4%), respectively. The DNA based PCR assays gave very high sensitivity (98.4%) but the specificity was comparatively low (75.3%). After enrichment, the high sensitivity and specificity was detected with SAMRT-II (78.8%) and SD-Cholera (99.1%), respectively. Considering PCR as the gold standard, the sensitivity and specificity of the RDTs remained between 52.3-58.2% and 92.3-96.8%, respectively. In the LCM, the sensitivity of direct and enrichment testing was high in SAMRT-II (88% and 92%, respectively), but the specificity was high in SD cholera for both the methods (97% and 100%, respectively). The sensitivity/specificity of RDTs and direct culture have also been analyzed considering the age, gender and diarrheal disease severity of the patients. Conclusion Overall, the performance of the RDT kits remained almost similar in terms of specificity and sensitivity. Performance of PCR was superior to the antibody-based RDTs. The RTDs are very useful in identifying cholera cases during outbreak/epidemic situations and for making them as a point-of-care (POC) testing tool needs more improvement.

Diarrhea is a leading contributor of mortality globally. To mitigate its disease burden, improved prognosis and alternative therapeutic approaches must be deployed. A cross-sectional gut microbiome analysis of 23 non-diarrheal and 5 diarrheal fecal samples was conducted with the aim of meeting the WHO's GAPPD (Global Action Plan for Pneumonia and Diarrhea) goals. Next-generation sequencing is a potent tool being increasingly used for epidemiological surveillance. It can help in the comparison of the structural diversity of the gut microbiome between diarrheal and non-diarrheal samples, thereby aiding in the identification of prospective prognostic and therapeutic candidates. The pilot study was designed to identify prospective taxa that were comparatively enriched in non-diarrheal samples and to predict gut microbial community interactions. 16S rRNA amplicon sequencing and subsequent analysis were undertaken for taxonomic profiling and abundance interpretation of OTUs. Significant differences between the two groups with respect to structural composition was revealed. Firmicutes was the most abundant phylum in the majority of the samples. The B/F ratio was consistently <1 in all diarrheal samples. A significant difference in the mean B/F ratio of the two groups was found. Proteobacteria was significantly more abundant in the diarrheal group. On the other hand, Prevotellaceae was the most abundant family in non-diarrheal samples and was suppressed significantly in diarrheal samples. Streptococcaceae was the most abundant family in 60% of diarrheal samples; where Streptococcaceae was suppressed, Bacteroideaceae and Nocardiaceae were the most abundant. In non-diarrheal samples, where Streptococcaceae was almost completely suppressed, Bifidobacteriaceae was the most abundant and significantly suppressed other families. A negative correlation was observed between Prevotellaceae and Bacteroideaceae in the non-diarrheal group. was the most abundant species in 70% of non-diarrheal samples and was significantly suppressed in diarrheal samples. was identified in all the non-diarrheal samples, while they were absent in diarrheal samples. The OTUs associated with diarrheal dysbiosis can serve as prognostic markers. To our knowledge, this is the first report on the comparative analysis of diarrheal and non-diarrheal microbiome, distinctly addressing the gut microbiome dysbiosis from the context that can lead to the development of prognostic markers and probiotics to protect the endemic population from diarrhea and help in achieving Sustainable Development Goals 2 and 3.

The human pathogen is the causative agent of severe diarrheal disease known as cholera. Of the more than 200 \"O\" serogroups of this pathogen, O1 and O139 cause cholera outbreaks and epidemics. The rest of the serogroups, collectively known as non-O1/non-O139 cause sporadic moderate or mild diarrhea and also systemic infections. Pathogenic circulates between nutrient-rich human gut and nutrient-deprived aquatic environment. As an autochthonous bacterium in the environment and as a human pathogen, maintains its survival and proliferation in these two niches. Growth in the gastrointestinal tract involves expression of several genes that provide bacterial resistance against host factors. An intricate regulatory program involving extracellular signaling inputs is also controlling this function. On the other hand, the ability to store carbon as glycogen facilitates bacterial fitness in the aquatic environment. To initiate the infection, must colonize the small intestine after successfully passing through the acid barrier in the stomach and survive in the presence of bile and antimicrobial peptides in the intestinal lumen and mucus, respectively. In , virulence is a multilocus phenomenon with a large functionally associated network. More than 200 proteins have been identified that are functionally linked to the virulence-associated genes of the pathogen. Several of these genes have a role to play in virulence and/or in functions that have importance in the human host or the environment. A total of 524 genes are differentially expressed in classical and El Tor strains, the two biotypes of serogroup O1. Within the host, many immune and biological factors are able to induce genes that are responsible for survival, colonization, and virulence. The innate host immune response to infection includes activation of several immune protein complexes, receptor-mediated signaling pathways, and other bactericidal proteins. This article presents an overview of regulation of important virulence factors in and host response in the context of pathogenesis.

A total of 178 strains of V. parahaemolyticus isolated from 13,607 acute diarrheal patients admitted in the Infectious Diseases Hospital, Kolkata has been examined for serovar prevalence, antimicrobial susceptibility and genetic traits with reference to virulence, and clonal lineages. Clinical symptoms and stool characteristics of V. parahaemolyticus infected patients were analyzed for their specific traits. The frequency of pandemic strains was 68%, as confirmed by group-specific PCR (GS-PCR). However, the prevalence of non-pandemic strains was comparatively low (32%). Serovars O3:K6 (19.7%), O1:K25 (18.5%), O1:KUT (11.2%) were more commonly found and other serovars such as O3:KUT (6.7%), O4:K8 (6.7%), and O2:K3 (4.5%) were newly detected in this region. The virulence gene tdh was most frequently detected in GS-PCR positive strains. There was no association between strain features and stool characteristics or clinical outcomes with reference to serovar, pandemic/non-pandemic or virulence profiles. Ampicillin and streptomycin resistance was constant throughout the study period and the MIC of ampicillin among selected strains ranged from 24 to >256 µg/ml. Susceptibility of these strains to ampicillin increased several fold in the presence of carbonyl cyanide-m-chlorophenyldrazone. The newly reported ESBL encoding gene from VPA0477 was found in all the strains, including the susceptible ones for ampicillin. However, none of the strains exhibited the β-lactamase as a phenotypic marker. In the analysis of pulsed-field gel electrophoresis (PFGE), the pandemic strains formed two different clades, with one containing the newly emerged pandemic strains in this region.

Background This is a unique and novel study delineating the genotyping and subsequent prediction of AMR determinants of Vibrio cholerae revealing the potential of contemporary strains to serve as precursors of severe AMR crisis in cholera. Methods and Results Genotyping of representative strains, VC1 and VC2 was undertaken to characterize antimicrobial resistance genes (ARGs) against chloramphenicol, SXT, nalidixic acid and streptomycin against which they were found to be resistant by antibiogram analysis in our previous investigation. strAB, sxt, sul2, qace∆1-sul1 were detected by PCR. Genome annotation and identification of ARGs with WGS helped to detect the presence of almG, varG, strA (APH(3'')-Ib), strB (APH(6)-Id), sul2, catB9, floR, CRP, dfrA1 genes. Signatures of resistance determinants and protein domains involved in antimicrobial resistance, primarily, efflux of antibiotics were identified on the basis of 30–100% homology to reference proteins. These domains were predicted to be involved in other metabolic functions on the basis of 100% identity with 100% coverage with reference protein and nucleotide sequences and were predicted to be of a diverse taxonomic origin accentuating the influence of the microbiota on AMR acquisition. Sequence analysis of QRDR (quinolone resistance-determining region) revealed SNPs. Cytoscape v3.8.2 was employed to analyse protein–protein interaction of MDR proteins, MdtA and EmrD-2, with nodes of vital AMR pathways. Vital nodes involved in efflux of different classes of antibiotics were found to be absent in VC1 and VC2 justifying the sensitivity of these strains to most antibiotics. Conclusions The study helped to examine the resistome of VC isolated from recent outbreaks to understand the underlying reason of sensitivity to most antibiotics and also to characterize the ARGs in their genome. It revealed that VC is a reservoir of signatures of resistance determinants and serving as precursors for severe AMR crisis in cholera. This is the first study, to our knowledge, which has scrutinized and presented systematically, information on prospective domains which bear the potential of serving as AMR determinants in VC with the help of bioinformatic tools. This pioneering approach may help in the prediction of AMR landfalls and benefit epidemiological surveillance and early warning systems.

Antimicrobial resistance (AMR) in bacteria is an important global health problem affecting humans, animals, and the environment. AMR is considered as one of the major components in the “global one health”. Misuse/overuse of antibiotics in any one of the segments can impact the integrity of the others. In the presence of antibiotic selective pressure, bacteria tend to develop several defense mechanisms, which include structural changes of the bacterial outer membrane, enzymatic processes, gene upregulation, mutations, adaptive resistance, and biofilm formation. Several components of mobile genetic elements (MGEs) play an important role in the dissemination of AMR. Each one of these components has a specific function that lasts long, irrespective of any antibiotic pressure. Integrative and conjugative elements (ICEs), insertion sequence elements (ISs), and transposons carry the antimicrobial resistance genes (ARGs) on different genetic backbones. Successful transfer of ARGs depends on the class of plasmids, regulons, ISs proximity, and type of recombination systems. Additionally, phage-bacterial networks play a major role in the transmission of ARGs, especially in bacteria from the environment and foods of animal origin. Several other functional attributes of bacteria also get successfully modified to acquire ARGs. These include efflux pumps, toxin-antitoxin systems, regulatory small RNAs, guanosine pentaphosphate signaling, quorum sensing, two-component system, and clustered regularly interspaced short palindromic repeats (CRISPR) systems. The metabolic and virulence state of bacteria is also associated with a range of genetic and phenotypic resistance mechanisms. In spite of the availability of a considerable information on AMR, the network associations between selection pressures and several of the components mentioned above are poorly understood. Understanding how a pathogen resists and regulates the ARGs in response to antimicrobials can help in controlling the development of resistance. Here, we provide an overview of the importance of genetic network and regulation of AMR in bacterial pathogens.

Cholera is a life-threatening infectious disease that remains an important public health issue in several low and middle-income countries. In 1992, a newly identified O139 Vibrio cholerae temporarily displaced the O1 serogroup. No study has been able to answer why the potential eighth cholera pandemic (8CP) causing V. cholerae O139 emerged so successfully and then died out. We conducted a genomic study, including 330 O139 isolates, covering emergence of the serogroup in 1992 through to 2015. We noted two key genomic evolutionary changes that may have been responsible for the disappearance of genetically distinct but temporally overlapping waves (A-C) of O139. Firstly, as the waves progressed, a switch from a homogenous toxin genotype in wave-A to heterogeneous genotypes. Secondly, a gradual loss of antimicrobial resistance (AMR) with the progression of waves. We hypothesize that these two changes contributed to the eventual epidemiological decline of O139. The O139 Vibrio cholerae serogroup emerged in the 1990s and spread rapidly but did not become globally dominant. Here, the authors describe the genomic epidemiology of this strain and identify changes in virulence and antimicrobial resistance characteristics that they hypothesise may have contributed to its decline.