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Introduction An acute gastrointestinal illness outbreak was reported in a higher educational institution among students and faculties in East Sikkim, India, from January to February 2023. The investigation was conducted to identify the source of the infection and causative pathogens and prevent the spread of the outbreak. Methods We defined a case as three or more loose stools in 24 hours, abdominal pain, or vomiting with the onset of symptoms between January 16 and February 16, 2023. Active surveillance was conducted by reviewing the affected individuals at the campus and patient registers at the dispensary, where cases were treated. Stool samples, rectal swabs, water samples, and suspected food samples were collected for microbiological testing using conventional culture, multiplex polymerase chain reaction (PCR), and kit-based real-time PCR methods. Results Out of 1,850 residents, 106 (5.7%) were affected by gastrointestinal symptoms like diarrhea, vomiting, etc. The attack rate for females was 23 (1.24%) and for males was 83 (4.49%). The most affected individual median age was 21 years (range: 2-51 years). From the laboratory investigations, most of the cases demonstrated polymicrobial etiologies. Gastroenteritis pathogens like Campylobacter, astrovirus, androtavirusdiarrheagenic Escherichia coli (DEC) (EAEC, EIEC, ETEC, EPEC, and EAEC), Shigella,etc., were detected in the suspected samples. The environmental investigation indicated the presence of rusted and leaky water pipes and sewage pipelines, along with ineffective chlorination of the water plant. Conclusions Based on epidemiological and laboratory investigations, it is conjectured that sewage and fecal contamination of drinking water and poor maintenance of the water distribution system most likely caused the outbreak described in this study. Basic treatment modalities, adequate chlorination, and periodic inspection of the water system were suggested, which controlled the outbreak to a greater extent.
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Food and waterborne outbreaks are a neglected public health problem in India. However, it is important to identify the source of infection and the causative pathogen to curb the outbreak quickly and minimize mortality and morbidity. A retrospective descriptive study was conducted with a line list of 130 diarrheal cases. Epidemiological investigation and laboratory investigation were done. Data were collected from hospital case report forms as well as interviewed affected cases. A case of acute diarrheal disease was reported among the people in the village with abdominal pain, vomiting, and diarrhea from December 31, 2022 to January 3, 2023. Out of a total of 130 recorded cases, 33 stool samples were collected and were positive for Enteroaggregative Escherichia coli, Shigella flexneri 3a, and Shigella sonnei by cultural and molecular tests. The presumptive fecal pollution indicator assay indicated high coliform counts in the water samples (most probable number [MPN]-05) and the presence of Escherichia coli. The identified pathogens showed susceptibility to gentamicin and meropenem. People who used public drinking water were found to be infected with acute diarrheal disease (ADD). Quick identification of the causative pathogens and their antimicrobial resistance pattern helped correct antibiotic prescriptions and quick recovery of the patients without any deaths. Thus, a timely implementation of food and waterborne outbreak investigation is crucial to saving lives and preventing the spread of infection.
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Survivin, a cancer-cell-specific multifunctional protein, is regulated by many oncogenic signaling pathways and an effective therapeutic target. Although, several types of survivin-targeting agents have been developed over the past few decades, none of them received clinical approval. This could be because survivin expression is tightly controlled by the feedback interaction between different signaling molecules. Of the several signaling pathways that are known to regulate survivin expression, the phosphatidylinositol 3-kinase/AKT serine-threonine kinase/forkhead boxO (PI3K/AKT/FoxO) pathway is well-known for feedback loops constructed by cross-talk among different molecules. Using sepantronium bromide (YM155), the first of its class of survivin-suppressant, we uncovered the existence of an interesting cross-talk between Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) and FoxO transcription factors that also contributes to YM155 resistance in triple negative breast cancer (TNBC) cells. Pharmacological manipulation to interrupt this interaction not only helped restore/enhance the drug-sensitivity but also prompted effective immune clearance of cancer cells. Because the YM155-induced reactive oxygen species (ROS) initiates this feedback, we believe that it will be occurring for many ROS-producing chemotherapeutic agents. Our work provides a rational explanation for the poor efficacy of YM155 compared to standard chemotherapy in clinical trials. Finally, the triple drug combination approach used herein might help reintroducing YM155 into the clinical pipeline, and given the high survivin expression in TNBC cells in general, it could be effective in treating this subtype of breast cancer.
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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.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Shigella , Criança , Humanos , Pré-Escolar , Escherichia coli Enterotoxigênica/genética , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/epidemiologia , Testes de Diagnóstico Rápido , Shigella/genética , Diarreia/diagnóstico , Diarreia/epidemiologiaRESUMO
BACKGROUND: 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. PRINCIPAL FINDINGS: 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 ß-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. CONCLUSION: 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.
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Antibacterianos , Farmacorresistência Bacteriana , Humanos , Prevalência , Antibacterianos/farmacologia , Cloranfenicol , Diarreia/epidemiologiaRESUMO
Foodborne gastroenteritis outbreaks owing to Salmonella enterica serovar Weltevreden (Salmonella Weltevreden) represent a significant global public health problem. In the past two decades, Salmonella Weltevreden has emerged as a dominant foodborne pathogen, especially in South-East Asian countries. This report describes a community foodborne outbreak of gastroenteritis caused by Salmonella Weltevreden in August 2022 following consumption of panipuri from a street vendor in the Polba block in Hooghly district, West Bengal, India. This food item was consumed by 185 people, of whom 129 had acute watery diarrhea with other clinical symptoms and 65 of them were admitted to different District hospitals for treatment. Stool specimens collected from hospitalized cases were positive for S. enterica, and further serotyped as Salmonella Weltevreden. All the Salmonella Weltevreden strains possessed the Salmonella pathogenicity islands associated genes (invA/E, orgA, ttrc, ssaQ, mgtC, misL, spi4D), the enterotoxin (stn), and hyperinvasive locus gene (hilA). Except erythromycin, all the strains were susceptible for commonly used antimicrobials in the treatment of diarrhea. The XbaI-based pulsed-field gel electrophoresis analysis indicated that all the isolates responsible for the recent outbreak were similar, but diverged from other Salmonella Weltevreden that were previously reported in West Bengal. This report indicates that foodborne infection is a major public health concern in India and demands to strengthen capacity-building measures at the local health care levels for linking causative agents of outbreaks.
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Gastroenterite , Salmonella enterica , Humanos , Sorogrupo , Salmonella enterica/genética , Salmonella , Gastroenterite/epidemiologia , Diarreia/epidemiologia , Surtos de Doenças , Índia/epidemiologia , Eletroforese em Gel de Campo PulsadoRESUMO
We isolated a Vibrio fluvialis strain (IDH5335) from a stool sample collected from a patient with diarrhea. In this announcement, we report the complete genomic sequence of this organism, which was obtained by combining Illumina and Oxford Nanopore sequencing data.
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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 12% more Shigella and 13% more 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.
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The oxidation-reduction reactions of disulfides are important in both chemistry and biology. Dimethyl disulfide (DMDS), the smallest reduced sulfur species with a disulfide bond, is emitted in significant quantities from natural sources and contributes to the formation of aerosols and hazardous haze. Although atmospheric removal of DMDS via the reactions with OH or NO3 radicals and photolysis is known, the reactions of DMDS with other atmospheric oxidants are yet to be explored. Herein, using quantum chemical calculations, we explored the reactions of DMDS with CH2OO (formaldehyde oxide) and other methyl-substituted Criegee intermediates. The various reaction pathways evaluated were found to have positive energy barriers. However, in the presence of formic acid, a direct oxygen-transfer pathway leading to the corresponding sulfoxide (CH3SS(O)CH3) was found to proceed through a submerged transition state below the separated reactants. Calculations for the methyl-substituted Criegee intermediates, particularly for anti-CH3CHOO, show a significant increase in the rate of the direct oxygen-transfer reaction when catalyzed by formic acid. The presence of formic acid also alters the mechanism and reduces the enthalpic barrier of a second pathway, forming thioformaldehyde and hydroperoxide without any rate enhancement. Our data indicated that, although Criegee intermediates are unlikely to be an important atmospheric sink of DMDS under normal conditions, in regions rich in DMDS and formic acid, the formic acid-catalyzed Criegee intermediate-mediated oxidation of DMDS via the direct oxygen-transfer pathway could lead to organic sulfur compounds contributing to atmospheric aerosol.
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Diarrhoeagenic Escherichia coli (DEC) pathotypes are one of the major causative agents of diarrhoea induced childhood morbidity and mortality in developing countries. Licensed vaccines providing broad spectrum protection against DEC mediated infections are not available. Outer membrane vesicles (OMVs) are microvesicles released by gram-negative bacteria during the growth phase and contain multiple immunogenic proteins. Based on prevalence of infections, we have formulated a pentavalent outer-membrane vesicles (POMVs) based immunogen targeting five main pathotypes of DEC responsible for diarrhoeal diseases. Following isolation, OMVs from five DEC pathotypes were mixed in equal proportions to formulate POMVs and 10 µg of the immunogen was intraperitoneally administered to adult BALB/c mice. Three doses of POMVs induced significant humoral immune response against whole cell lysates (WCLs), outer membrane proteins (OMPs) and lipopolysaccharides (LPS) isolated from DEC pathotypes along with significant induction of cellular immune response in adult mice. Passive transfer of POMVs immunized adult mice sera protected neonatal mice significantly against DEC infections. Overall, this study finds POMVs to be immunogenic in conferring broad-spectrum passive protection to neonatal mice against five main DEC pathotypes. Altogether, these findings suggest that POMVs can be used as a potent vaccine candidate to ameliorate the DEC-mediated health burden.
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Diarreia , Lipopolissacarídeos , Humanos , Adulto , Animais , Camundongos , Criança , Animais Recém-Nascidos , Imunidade Humoral , Escherichia coliRESUMO
Aim: To characterize extensively drug-resistant Pseudomonas aeruginosa from a patient with diarrhea. Materials & methods: Antimicrobial susceptibility was tested by the disk diffusion method. The P. aeruginosa genome was sequenced to identify virulence, antibiotic resistance and prophages encoding genes. Results: P. aeruginosa had a wide spectrum of resistance to antibiotics. Genomic analysis of P. aeruginosa revealed 76 genes associated with antimicrobial resistance, xenobiotic degradation and the type three secretion system. Conclusion: This is the first report on diarrhea associated with P. aeruginosa. Since no other organism was identified, the authors assume that the patient had dysbiosis due to antibiotic exposure, leading to antibiotic-associated diarrhea. The in vivo toxicity expressed by the pathogen may be associated with T3SS.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Genômica , Virulência/genética , Diarreia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade MicrobianaRESUMO
Many patients with cholera emerge in Kolkata, India throughout the year. Such emergency indicates that cholera toxin-producing Vibrio cholerae O1 (toxigenic V. cholerae O1) are widespread in Kolkata. This suggests that the suitable conditions for replication of toxigenic V. cholerae O1 is provided in Kolkata. In previous studies, we found that the replication rate of toxigenic V. cholerae O1 is low in the low ionic aqueous solution. Then we measured the ion concentration in the environmental water of Kolkata. As a control, we measured them in Japanese environmental water. The ion concentration in the environmental water of Kolkata was significantly high. Then, we examined the survival of toxigenic V. cholerae O1 in groundwater from Kolkata and found that V. cholerae O1 survive for long time in the solution but not in the solution diluted with Milli Q water. In addition, we found that V. cholerae O1 proliferated in environmental water of Kolkata to which a small amount of nutrient was added, but did not grow in the environmental water diluted with water to which the same amount of nutrient was added. These results indicate that the environmental water from Kolkata is suitable for survival of V. cholerae O1.
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Vibrio cholerae O1 , Microbiologia da Água , Toxina da Cólera , Índia , Água Subterrânea/microbiologiaRESUMO
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.
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Redes Reguladoras de Genes , Sistemas Toxina-Antitoxina , Animais , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Bactérias/genéticaRESUMO
We examined the stools of 23 patients in Kolkata, who were diagnosed as cholera patients because Vibrio cholerae O1 was detected from their stools by culturing methods, and further explored by metagenomic sequencing analysis. Subsequently, the presence of the gene encoding A subunit of cholera toxin (ctxA) and the cholera toxin (CT) level in these stool samples were examined. ctxA was examined by both metagenomic sequencing analysis and polymerase chain reaction. In these examinations, two samples did not show positive in any of these tests. The metagenomic analysis showed that the genes for Streptococcus pneumoniae and Salmonella enterica were present in the stools of these two patients, respectively. Therefore, these two patients were not considered to have diarrhea due to V. cholerae infection. From these results, we predicted that some Kolkata residents harbor a small number of V. cholerae in their intestines as a form of subclinical infection with V. cholerae. Next, we analyzed the stool samples of 22 diarrhea patients from which V. cholerae was not isolated. The results showed that 3 of the patients seemed to have subclinical infection of V. cholerae based on the amount of the genes. These results indicated that subclinical infections with V. cholerae O1 occur in Kolkata.
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Cólera , Vibrio cholerae O1 , Humanos , Vibrio cholerae O1/genética , Infecções Assintomáticas , Toxina da Cólera/genética , Cólera/diagnóstico , Cólera/epidemiologia , Diarreia/epidemiologia , Índia/epidemiologiaRESUMO
The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a global health crisis. The ability of vaccines to protect immunocompromised individuals and from emerging new strains are major concerns. Hence antiviral drugs against SARS-CoV-2 are essential. The SARS-CoV-2 main protease Mpro is vital for replication and an important target for antivirals. Using CMap analysis and docking studies, withaferin A (wifA) and withanone (win), two natural products from the medicinal herb Withania somnifera (ashwagandha), were identified as promising candidates that can covalently inhibit the viral protease Mpro. Cell culture, enzymatic, LC-MS/MS, computational, and equilibrium dialysis based assays were performed. DFT calculations indicated that wifA and win can form stable adducts with thiols. The cytotoxicity of Mpro was significantly reduced by wifA and win. Both wifA and win were found to irreversibly inhibit 0.5 µM Mpro with IC50 values of 0.54 and 1.8 µM, respectively. LC-MS/MS analysis revealed covalent adduct formation with wifA at cysteines 145 and 300 of Mpro. The natural products wifA and win can irreversibly inhibit the SARS-CoV-2 main protease Mpro. Based on the work presented here we propose that both wifA and win have the potential to be safely used as preventative and therapeutic interventions for COVID-19.
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Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Plantas Medicinais , Withania , Humanos , Produtos Biológicos/farmacologia , Cromatografia Líquida , Cisteína Endopeptidases , Simulação de Acoplamento Molecular , Pandemias , Inibidores de Proteases/farmacologia , SARS-CoV-2 , Espectrometria de Massas em Tandem , Proteínas não Estruturais ViraisRESUMO
AIMS: The present study aimed to document the comparative analysis of differential hypervirulent features of Vibrio cholerae O1 strains isolated during 2018 from cholera endemic regions in Gujarat and Maharashtra (Western India) and West Bengal (Eastern India). METHODS AND RESULTS: A total of 87 V. cholerae O1 clinical strains from Western India and 48 from Eastern India were analysed for a number of biotypic and genotypic features followed by antimicrobial resistance (AMR) profile. A novel polymerase chain reaction was designed to detect a large fragment deletion in the Vibrio seventh pandemic island II (VSP-II) genomic region, which is a significant genetic feature of the V. cholerae strains that have caused Yemen cholera outbreak. All the strains from Western India belong to the Ogawa serotype, polymyxin B-sensitive, hemolytic, had a deletion in VSP-II (VSP-IIC) region and carried Haitian genetic alleles of ctxB, tcpA and rtxA. Conversely, 14.6% (7/48) of the strains from Eastern India belonged to the Inaba serotype, polymyxin B-resistant, nonhemolytic, harboured VSP-II other than VSP-IIC type, classical ctxB, Haitian tcpA and El Tor rtxA alleles. Resistance to tetracycline and chloramphenicol has been observed in strains from both regions. CONCLUSIONS: This study showed hypervirulent, polymyxin B-sensitive epidemic causing strains in India along with the strains with polymyxin B-resistant and nonhemolytic traits that may spread and cause serious disease outcomes in future. SIGNIFICANCE AND IMPACT OF THE STUDY: The outcomes of this study can help to improve the understanding of the hyperpathogenic property of recently circulating pandemic Vibrio cholerae strains in India. Special attention is also needed for the monitoring of AMR surveillance because V. cholerae strains are losing susceptibility to many antibiotics used as a second line of defence in the treatment of cholera.
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Cólera , Vibrio cholerae O1 , Humanos , Vibrio cholerae O1/genética , Cólera/epidemiologia , Cólera/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Polimixina B/farmacologia , Haiti , Farmacorresistência Bacteriana/genética , Índia/epidemiologia , Genótipo , Surtos de Doenças , Toxina da Cólera/genética , Toxina da Cólera/uso terapêuticoRESUMO
Purpose: The multidrug resistance Enterobacteriaceae cause many serious infections resulting in prolonged hospitalization, increased treatment charges and mortality rate. In this study, we characterized bla NDM-5-positive multidrug resistance commensal Escherichia coli (CE) isolated from diarrheal patients in Kolkata, India. Methods: Three CE strains were isolated from diarrheal stools, which were negative for different pathogroups of diarrheagenic E. coli (DEC). The presence of carbapenemases encoding genes and other antimicrobial resistance genes (ARGs) was detected using PCR. The genetic arrangement adjoining bla NDM-5 was investigated by plasmid genome sequencing. The genetic relatedness of the strains was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) methods. Results: In addition to colistin, the bla NDM-5-positive CE strains showed resistance to most of the antibiotics. Higher MICs were detected for ciprofloxacin (>32 mg/L) and imipenem (8 mg/L). Molecular typing revealed that three CE strains belonged to two different STs (ST 101 and ST 648) but they were 95% similar in the PFGE analysis. Screening for ARGs revealed that CE strains harbored Int-1, bla TEM, blaC TX-M3, bla OXA-1, bla OXA-7, bla OXA-9, tetA, strA, aadA1, aadB, sul2, floR, mph(A), and aac(6´)-Ib-cr. In conjugation experiment, transfer frequencies ranged from 2.5×10-3 to 8.4x10-5. The bla NDM-5 gene was located on a 94-kb pNDM-TC-CE-89 type plasmid, which is highly similar to the IncFII plasmid harboring an IS26-IS30-bla NDM-5-ble MBL-trpF-dsbd-IS91-dhps structure. Conclusion: To the best of our knowledge, this is the first report on carbapenem resistance involving the bla NDM-5 gene in CE from diarrheal patients. The circulation of bla NDM-5 gene in CE is worrisome, since it has the potential to transfer bla NDM-5 gene to other enteric pathogens.
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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.
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Cólera , Vibrio cholerae O139 , Vibrio cholerae , Cólera/epidemiologia , Toxina da Cólera/genética , Humanos , Pandemias , Vibrio cholerae/genética , Vibrio cholerae O139/genéticaRESUMO
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-ß-(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.
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AIMS: This study analyses the prevalence and antimicrobial resistance (AMR) of major diarrhoeagenic Escherichia coli (DEC) pathotypes detected in hospitalized diarrhoeal patients in Kolkata, India, during 2012-2019. METHODS AND RESULTS: A total of 8891 stool samples were collected from the Infectious Diseases Hospital, Kolkata and screened for the presence of enteric pathogens. Multiplex PCR identified the presence of DEC in 7.8% of the samples, in which ETEC was most common (47.7%) followed by EAEC (38.4%) and EPEC (13.9%). About 54% cases were due to sole DEC infections. Majority of the mixed DEC infections were caused by the Vibrio spp. (19.1%) followed by Rotavirus (14.1%) and Campylobacter spp. (8.4%). ETEC and EAEC were associated significantly with diarrhoea in children <5 years of age, whereas EPEC and also ETEC were prevalent in patients aged between 5 and 14 years. AMR profile showed high prevalence of multidrug resistance (MDR) among DEC (56.9%) in which 9% were resistant to antibiotics of six different antimicrobial classes. Screening of the AMR conferring genes of DEC showed the presence of blaCTX-M3 (30.2%) in highest number followed by blaTEM (27.5%), tetB (18%), sul2 (12.6%), strA (11.8%), aadA1 (9.8%), blaOXA-1 (9%), dfrA1 (1.6%) and blaSHV (1.2%). CONCLUSIONS: These findings highlighted the high prevalence of MDR in major DEC pathotypes that could be considered as the leading aetiological bacterial agent responsible for diarrhoea and suggests a significant public health threat. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study can help to improve the understanding of the epidemiology of DEC infections in patients with diarrhoea. Monitoring of AMR surveillance needs special attention because the DEC isolates were highly resistant to commonly used antimicrobials in the treatment of diarrhoea.