Therapeutic Approaches to Combat the Global Antibiotic Resistance Challenge

Farhat, Nabeela; Khan, Asad U.

doi:10.2217/fmb-2022-0052

Cited by 7 publications

(4 citation statements)

References 80 publications

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“…The emergence of beta-lactamases such as bla NDM , extended spectrum beta lactamases (ESBLs) such as bla CTX-M , bla SHV , and bla TEM etc. has led to the use of last resort antibiotics such as tigecycline, polymyxin E, daptomycin, vancomycin and linezolid [ 84 – 86 ]. However, in the last decade several ARGs against the last-line antibiotics have been reported [ 87 – 93 ].…”

Section: Discussionmentioning

confidence: 99%

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Talat,

Khan,

Khan

2024

BMC Microbiol

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Background Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT). Results This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 μg/mL), while broth microdilution identified 48 (MIC = 32–128 μg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated blaNDM-5 (K. pneumoniae ST147) and chromosomally mediated blaNDM-1 (P. aeruginosa ST357). Conclusion The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance.

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Section: Discussionmentioning

confidence: 99%

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Talat,

Khan,

Khan

2024

BMC Microbiol

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“…Recent evidences have showed that antibiotic combination therapy provides an effective solution to antibiotic resistance (Coates et al., 2020 ; Farhat and Khan, 2022 ; Scudeller et al., 2021 ). However, how these antibiotics work together and how their underlying mechanisms operate are being explored.…”

Section: Discussionmentioning

confidence: 99%

Elevated proton motive force is a tetracycline resistance mechanism that leads to the sensitivity to gentamicin in Edwardsiella tarda

Li,

Xiang,

Zeng

et al. 2023

Microbial Biotechnology

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Tetracycline is a commonly used human and veterinary antibiotic that is mostly discharged into environment and thereby tetracycline‐resistant bacteria are widely isolated. To combat these resistant bacteria, further understanding for tetracycline resistance mechanisms is needed. Here, GC–MS based untargeted metabolomics with biochemistry and molecular biology techniques was used to explore tetracycline resistance mechanisms of Edwardsiella tarda. Tetracycline‐resistant E. tarda (LTB4‐RTET) exhibited a globally repressed metabolism against elevated proton motive force (PMF) as the most characteristic feature. The elevated PMF contributed to the resistance, which was supported by the three results: (i) viability was decreased with increasing PMF inhibitor carbonylcyanide‐3‐chlorophenylhydrazone; (ii) survival is related to PMF regulated by pH; (iii) LTB4‐RTET were sensitive to gentamicin, an antibiotic that is dependent upon PMF to kill bacteria. Meanwhile, gentamicin‐resistant E. tarda with low PMF are sensitive to tetracycline is also demonstrated. These results together indicate that the combination of tetracycline with gentamycin will effectively kill both gentamycin and tetracycline resistant bacteria. Therefore, the present study reveals a PMF‐enhanced tetracycline resistance mechanism in LTB4‐RTET and provides an effective approach to combat resistant bacteria.

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“…Carvacrol is monoterpenoid phenol that has profound antibacterial activity and it alters the membrane permeability so, combination therapy using Topoisomerase inhibitors and plant-based nanoparticles may be an alternate treatment for resistant bacteria ( Marinelli et al, 2018 ). Combination therapy is a strategy that combines two or more therapeutic drugs to achieve synergism, dose reduction and protection from bacterial resistance ( Farhat and Khan 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic antibacterial activity of carvacrol loaded chitosan nanoparticles with Topoisomerase inhibitors and genotoxicity evaluation

Akhlaq

Ashraf

Omer

et al. 2023

Saudi Journal of Biological Sciences

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Therapeutic Approaches to Combat the Global Antibiotic Resistance Challenge

Cited by 7 publications

References 80 publications

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings

Elevated proton motive force is a tetracycline resistance mechanism that leads to the sensitivity to gentamicin in Edwardsiella tarda

Synergistic antibacterial activity of carvacrol loaded chitosan nanoparticles with Topoisomerase inhibitors and genotoxicity evaluation

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