The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and ...controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two β-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the β-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.
The emergence of multidrug-resistant
poses a global threat, but the distribution and resistance profiling are unclear, especially in young children. Infections due to
are common, associated with high ...mortality, and increasingly β-lactam drug resistant.
We studied the molecular epidemiology and antibiotic resistance mechanisms in 294 clinicalisolates of
from a pediatric hospital in China. Non-duplicate isolates were recovered from clinical cases and were identified using an API-20 kit followed by antimicrobial susceptibility testing using the VITEK®2 compact system (BioMerieux, France) and also by broth dilution method. In addition, a double-disc synergy test for the ESBL/E-test for MBL was performed. The presence of beta-lactamases, plasmid types, and sequence types was determined by PCR and sequencing.
Fifty-six percent (
= 164) of the isolates were resistant to piperacillin-tazobactam, followed by cefepime (40%;
= 117), ceftazidime (39%;
= 115), imipenem (36%;
= 106), meropenem (33%;
= 97), and ciprofloxacin (32%;
= 94). Forty-two percent (n = 126) of the isolates were positive for ESBL according to the double-disc synergy test. The blaCTX-M-15 cephalosporinase was observed in 32% (n = 40/126), while 26% (n = 33/126) werepositive for blaNDM-1 carbapenemase. Aminoglycoside resistance gene
was observed in 16% (n = 20/126), and glycylcyclines resistance gene tet(A) was observed in 12% (n = 15/126) of the isolates. A total of 23 sequence types were detected, including ST1963 (12%; n = 16), followed by ST381 (11%;
= 14), ST234 (10%;
= 13), ST145 (58%;
= 10), ST304 (57%;
= 9), ST663 (5%; n = 7), and a novel strain. In ESBL-producing
, 12 different Incompatibility groups (Inc) were observed, the most common being IncFI, IncFIS, and IncA/C. The MOBP was the most common plasmid type, followed by MOBH, MOBF, and MOBQ.
Our data suggest that the spread of antibiotic resistance is likely due toclonal spread and dissemination of different clinical strains of
harbouring different plasmids. This is a growing threat in hospitals particularly in young children which needs robust prevention strategies.
Carbapenem-resistant
is an opportunistic pathogen responsible for nosocomial infections and is one of the biggest global threats according to the World Health Organization (WHO), particularly causing ...substantial morbidity and mortality.
This study aimed at using computational approaches to screen meropenem and its analogs against OXA-23-positive
analyzing the correlations between kinetic and phenotypic characteristics.
A total of 5,450 compounds were screened using virtual screening workflow (HTVS, Glide-SP, and Glide-XP) to identify the best compounds based on their binding energy and interactions against OXA-23 and OXA-27 as they had phenotypic data available. Molecular dynamics simulation and density functional theory (DFT) studies were performed from the outcome of molecular docking analysis.
During simulations, meropenem and its analogs exhibited high-level stable interactions with Ser79, Ser126, Thr217, Trp219, and Arg259 of OXA-23. Meropenem displayed a CovDock energy of about -3.5 and -1.9 kcal mol
against OXA-23 and OXA-27, respectively. Among the 5,450 compounds, Pubchem_10645796, Pubchem_25224737, and ChEMBL_14 recorded CovDock energy between -6.0 and -9.0 kcal mol
. Moreover, the infra-red (IR) spectrophotometric analysis revealed C=O and C-N atoms showing bands at 1,800 and 1,125 cm
, respectively. These observed data are in congruence with the experimental observations.
The identified compounds showed good agreement with the spectrophotometric analysis using DFT methods. In the earlier studies, meropenem's MIC value was 32 μg mL
in OXA-23-positive isolate A2265 compared to the MIC of 1 μg mL
in Δ
A2265. Comparing the CovDock energy and hydrogen-bonding interactions, the predicted results are in good agreement with the experimental data reported earlier. Our results highlight the importance of OXA-23 molecular docking studies and their compliance with the phenotypic results. It will help further in developing newer antibiotics for treating severe infections associated with carbapenem-resistant
.
The emergence of virulent extended spectrum β-lactamase producing Klebsiella pneumoniae (ESBL-KP) including carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired infections has ...resulted in significant morbidity and mortality worldwide. We investigated the antibiotic resistance and virulence factors associated with ESBL-KP and CRKP in tertiary care hospitals in Bangladesh and explored their ability to form biofilm. A total of 67 ESBL-KP were isolated from 285 Klebsiella pneumoniae isolates from environmental and patient samples from January 2019 to April 2019. For ESBL-KP isolates, molecular typing was carried out using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), antibiotic susceptibility testing, PCR for virulence and drug-resistant genes, and biofilm assays were also performed. All 67 isolates were multidrug-resistant (MDR) to different antibiotics at high levels and 42 isolates were also carbapenem-resistant. The most common β-lactam resistance gene was blaCTX-M-1 (91%), followed by blaTEM (76.1%), blaSHV (68.7%), blaOXA-1 (29.9%), blaGES (14.9%), blaCTX-M-9 (11.9%), and blaCTX-M-2 (4.5%). The carbapenemase genes blaKPC (55.2%), blaIMP (28.4%), blaVIM (14.9%), blaNDM-1 (13.4%), and blaOXA-48 (10.4%) and virulence-associated genes such as fimH (71.6%), ugeF (58.2%), wabG (56.7%), ureA (47.8%) and kfuBC (28.4%) were also detected. About 96.2% of the environmental and 100% of the patient isolates were able to form biofilms. ERIC-PCR-based genotyping and hierarchical clustering of K. pneumoniae isolates revealed an association between environmental and patient samples, indicating clonal association with possible transmission of antimicrobial resistance genes. Our findings can help in improving patient care and infection control, and the development of public health policies related to hospital-acquired infections.
The emergence of bacterial pathogens in environmental hosts represents a major risk to public health. This study aimed at characterizing seven novel environmental strains of
using a genomic approach ...which was misidentified by phenotypic methods in a previous batch of 27 species thought to be
.
Whole-genome sequencing was performed using the Illumina platform, and the generated raw reads were
assembled. Comparative genomic, resistome, virulome, mobilome, and phylogeny were then investigated using dierent bioinformatics tools.
Six strains were identified as
subsp
and one as
subsp.
. All isolates were resistant to ampicillin, cephalexin, and amoxicillin-clavulanic acid and harbored the
,
types,
, and
genes. One isolate additionally harbored a gene cassettes consisting of
,
,
'
genes. The aminoglycoside-modifying enzyme gene
was bracketed by two insertion elements. Plasmid analyses showed that IncFIB
was the most prevalent plasmid, circulating in six isolates, while one isolate exhibited seven different plasmids. The isolates have virulence genes responsible for capsule formation, lipopolysaccharide, iron uptake aerobactin (
), salmochelins (
), enterobactin siderophore, adherence, and biofilm formation (
, and
).
Our study highlights the ecology and transmission of
(which have the ability to disseminate to other environmental sources including animals) outside the clinical setting and the contribution of water, vegetables, and table surfaces as potential reservoirs of farm-to-fork transmission of disease via local markets in Khartoum, Sudan.
The epidemiological and clinical aspects of coronavirus disease-2019 (COVID-19) have been subjected to several investigations, but little is known about symptomatic patients with negative SARS-CoV-2 ...PCR results. The current study investigated patients who presented to the hospital with respiratory symptoms (but negative SARS-CoV-2 RT-PCR results) to determine the prevalence of bacterial pathogens among these patients. A total of 1246 different samples were collected and 453 species of bacterial pathogens were identified by culture. Antibiotic susceptibility testing was performed via the Kirby Bauer disc diffusion test. Patients showed symptoms, such as fever (100%), cough (83%), tiredness (77%), loss of taste and smell (23%), rigors (93%), sweating (62%), and nausea (81%), but all tested negative for COVID-19 by PCR tests. Further examinations revealed additional and severe symptoms, such as sore throats (27%), body aches and pain (83%), diarrhea (11%), skin rashes (5%), eye irritation (21%), vomiting (42%), difficulty breathing (32%), and chest pain (67%). The sum of n = 1246 included the following: males, 289 were between 5 and 14 years, 183 (15–24 years), 157 (25–34 years), 113 (35–49 years), and 43 were 50+ years. Females: 138 were between 5 and 14 years, 93 (15–24 years), 72 (25–34 years), 89 (35–49 years), and 68 were 50+ years. The Gram-positive organisms isolated were Staphylococcus aureus (n = 111, 80.43%, MRSA 16.6%), E. faecalis (n = 20, 14.49%, VRE: 9.4%), and Streptococcus agalactiae (n = 7, 5.07%), while, Gram-negative organisms, such as E. coli (n = 135, 42.85%, CRE: 3.49%), K. pneumoniae (n = 93, 29.52%, CRE: 1.58%), P. aeruginosa (n = 43, 13.65%), C. freundii (n = 21, 6.66%), Serratia spp. (n = 8, 2.53%), and Proteus spp. (n = 15, 4.76%) were identified.
Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of ...multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009.
Multiplex PCR was used to identify the main resistance genes in 15 multi-resistant A. baumannii isolates. RT-PCR was used to measure gene expression. The genetic environment of these genes was also analysed by PCR amplification and sequencing. Minimum inhibitory concentrations were determined for key antibiotics and some were determined in the presence of an efflux pump inhibitor, 1-(1-napthylmethyl) piperazine.
Fourteen strains were found to be multi-resistant. Each strain was found to have the blaOXA-58 gene with the ISAba3-like element upstream, responsible for over-expression of the latter and subsequent carbapenem resistance. Similarly, ISAba1, upstream of the blaADC gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance. In addition, the adeA, adeB efflux genes were over-expressed. All 15 isolates were positive for at least two aminoglycoside resistance genes.
This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of theblaOXA-58, blaADC and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA topoisomerases are responsible for the multi-resistance of the bacteria and the subsequent difficulty in treating infections caused by them.
The genus Bacillus constitutes a plethora of species that have medical, environmental, and industrial applications. While genus Bacillus has been the focus of several studies where genomic data have ...been used to resolve many taxonomic issues, there still exist several ambiguities. Through the use of in-silico genome-based methods, we tried to resolve the taxonomic anomalies of a large set of Bacillus genomes (n = 178). We also proposed species names for uncharacterized strains and reported genome sequence of a novel isolate Bacillus sp. RL. In the hierarchical clustering on genome-to-genome distances, we observed 11 distinct monophyletic clusters and investigated the functional pathways annotated as the property of these clusters and core-gene content of the entire dataset. Thus, we were able to assert the possible outlier strains (n = 17) for this genus. Analyses of secondary metabolite potential of each strain helped us unravel still unexplored diversity for various biosynthetic genes.
•Whole genome-based phylogeny using in-silico methods•Revisiting the current taxonomic classifications of a large set of Bacillus genomes•Genome sequence of a novel isolate of genus Bacillus•Assertion of possible outliers based on phylogeny and core-gene content•Analyses of secondary metabolite potential for commercial applications
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