scholarly journals Emergence of plasmid-mediated mcr genes from Gram-negative bacteria at the human-animal interface

Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Humera Javed ◽  
Sidrah Saleem ◽  
Aizza Zafar ◽  
Aamir Ghafoor ◽  
Ahmad Bin Shahzad ◽  
...  

Abstract Background The global emergence of plasmid-mediated colistin resistance (Col-R) conferred by mcr genes in gram-negative rods (GNRs) has jeopardized the last treatment option for multidrug-resistant bacterial infections in humans. This study aimed to assess the emergence of mcr gene-mediated Col-R in GNRs isolated from humans and animals in Pakistan. Methods Animal and clinical specimens collected from various sources were prospectively analysed using standard microbiological procedures. Pathogens were identified using the API 20E and API 20NE systems (bioMerieux). Minimum inhibitory concentration (MIC) against colistin was determined using the MIC detection methods, and multiplex polymerase chain reaction (PCR) was used to amplify the mcr-1 to mcr-5 genes. Results We isolated 126 (88.1%) animal and 17 (11.9%) human Col-R phenotypes, among which there was a significant association (P < 0.01) of Escherichia coli and Proteus mirabilis with animals and of Acinetobacter baumannii with humans. Animal strains exhibited statistically significant (P < 0.05) resistance to co-trimoxazole, chloramphenicol, and moxifloxacin, and the human pathogens exhibited statistically significant (P < 0.05) antibiotic resistance to cephalosporins, carbapenems, and piperacillin-tazobactam. For Col-R strains, MIC50 values were > 6 µg/mL and > 12 µg/mL for human and animal isolates, respectively. mcr genes were detected in 110 (76.9%) bacterial strains, of which 108 (98.2%) were mcr-1 and 2 (1.8%) were mcr-2. Conclusions The detection of a considerable number of mcr-1 and mcr-2 genes in animals is worrisome, as they are now being detected in clinical pathogens. The acquisition of mcr genes by colistin-susceptible bacteria could leave us in a post-antibiotic era.

2021 ◽  
Vol 14 (2) ◽  
pp. 185-196
Author(s):  
Jatin Chadha ◽  
Manish Gupta ◽  
Nishtha Nagpal ◽  
Madhav Sharma ◽  
Tarun Adarsh ◽  
...  

The extensive use of antibiotics to treat bacterial infections has led to the widespread emergence of multidrug-resistant (MDR) pathogens, becoming increasingly difficult to treat with currently available antibacterial agents. The present study is based on prospecting the ethnomedicinal potential of Indian plant varieties for the treatment of MDR bacteria. Plants produce an array of diverse pharmacological compounds in defence against microbial pathogens which may be employed as a novel intervention strategy to combat MDR human pathogens. In the present study, the antimicrobial activity of extracts of four common Indian plants: Azadirachta indica (Neem), Murraya koenigii (Kadipatta), Phyllanthus emblica (Amla), and Ocimum sanctum (Tulsi) prepared in four solvents, water, methanol, ethanol, and chloroform was tested against nine MDR bacterial isolates. Kirby-Bauer well diffusion assays were adopted to assess the antimicrobial activity of plant extracts against the MDR strains. The potency of plant extracts was examined by determining the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). All MDR isolates including Staphylococcus haemolyticus, Bacillus subtilis, B. thuringiensis, B. cereus, Enterobacter xiangfangensis, Klebsiella pneumoniae, and Pseudomonas aeruginosa were significantly inhibited by the plant extracts. Test extracts showed promising antibacterial potential against MDR P. aeruginosa and Bacillus sp. with low MIC values ranging between 0.02-1.56 mg/ml, while most plant extracts exhibited either moderate MBC values or bacteriostatic effects. To the best of our knowledge, this is the first study that demonstrates the potential use of endemic A. indica, M. koenigii, P. emblica, and O. sanctum as therapeutic agents against circulating MDR human pathogens in the national capital.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 774
Author(s):  
Martijn Zwama ◽  
Kunihiko Nishino

The rise in multidrug resistance (MDR) is one of the greatest threats to human health worldwide. MDR in bacterial pathogens is a major challenge in healthcare, as bacterial infections are becoming untreatable by commercially available antibiotics. One of the main causes of MDR is the over-expression of intrinsic and acquired multidrug efflux pumps, belonging to the resistance-nodulation-division (RND) superfamily, which can efflux a wide range of structurally different antibiotics. Besides over-expression, however, recent amino acid substitutions within the pumps themselves—causing an increased drug efflux efficiency—are causing additional worry. In this review, we take a closer look at clinically, environmentally and laboratory-evolved Gram-negative bacterial strains and their decreased drug sensitivity as a result of mutations directly in the RND-type pumps themselves (from Escherichia coli, Salmonella enterica, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Acinetobacter baumannii and Legionella pneumophila). We also focus on the evolution of the efflux pumps by comparing hundreds of efflux pumps to determine where conservation is concentrated and where differences in amino acids can shed light on the broad and even broadening drug recognition. Knowledge of conservation, as well as of novel gain-of-function efflux pump mutations, is essential for the development of novel antibiotics and efflux pump inhibitors.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Victorien Dougnon ◽  
Vincentia Marie Camille Houssou ◽  
Eugénie Anago ◽  
Chimène Nanoukon ◽  
Jibril Mohammed ◽  
...  

Gram-negative bacilli can spread from the environment and through food products. This study aimed to characterize ESBL production and virulence genes from multidrug-resistant Gram-negative bacilli isolated from specimen collected from the environment, kitchen, and food products. A total of 130 samples were collected at local markets in seven different communities in Benin (Abomey-Calavi, Ouidah, Bohicon, Abomey, Parakou, Djougou, and Grand-Popo). Samples were cultured on McConkey and ChromID™ ESBL agar plates. The isolates were identified by the API 20E gallery. An antibiotic susceptibility test was carried out, and the detection of ESBL production and virulence-associated genes was carried out by Polymerase Chain Reaction (PCR). The data collected was coded and analyzed using GraphPad prism 7 software and Excel. The software R was used to calculate the correlation coefficient between the results of the detection of ESBL+ on agar and by the effect of the double synergy. The results showed that sixty-three (63) bacterial strains were isolated from the 130 samples, of which the dominant species was Chryseomonas luteola (10/63). The kitchen samples were the most contaminated with 36.50%. More than 40% of the isolates were resistant to at least three different classes of antibiotics. Also, blaSHV gene was detected in 33.33% (21/63) of the isolates and in all isolates of Pseudomonas aeruginosa (5/5%). 11.11% (7/63) of isolates were virulent with dominance of the fimH gene, especially with Escherichia coli (83.33%). The kitchen samples showed a high prevalence of ESBL-producing strains with fimH gene. This raises the problem of non-compliance with hygiene rules in community cooking and food handling.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Li Liu ◽  
Jingyi Yu ◽  
Xiaofei Shen ◽  
Xingwei Cao ◽  
Qing Zhan ◽  
...  

Abstract Background Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect. Results MIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria. Conclusions Our in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.


2019 ◽  
Vol 69 (Supplement_6) ◽  
pp. S466-S473 ◽  
Author(s):  
Oluwafemi Popoola ◽  
Aderemi Kehinde ◽  
Veronica Ogunleye ◽  
Oluwafemi J Adewusi ◽  
Trevor Toy ◽  
...  

Abstract Background The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. Methods Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. Results A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. Conclusions The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.


mBio ◽  
2022 ◽  
Author(s):  
Anne Lanois-Nouri ◽  
Lucile Pantel ◽  
Jun Fu ◽  
Jessica Houard ◽  
Jean-Claude Ogier ◽  
...  

Odilorhabdins (ODLs) constitute a novel antibiotic family with promising properties for treating problematic multidrug-resistant Gram-negative bacterial infections. ODLs are 10-mer linear cationic peptides inhibiting bacterial translation by binding to the small subunit of the ribosome.


2021 ◽  
Vol 7 ◽  
Author(s):  
Rémy A. Bonnin ◽  
Agnès B. Jousset ◽  
Cécile Emeraud ◽  
Saoussen Oueslati ◽  
Laurent Dortet ◽  
...  

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Oumer Abdu Muhie

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.


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