Inverse Association between the Existence of CRISPR/Cas Systems with Antibiotic Resistance, Extended Spectrum β-Lactamase and Carbapenemase Production in Multidrug, Extensive Drug and Pandrug-Resistant Klebsiella pneumoniae

Jwair, Noor A.; Al-Ouqaili, Mushtak T. S.; Al-Marzooq, Farah

doi:10.3390/antibiotics12060980

Cited by 18 publications

(17 citation statements)

References 51 publications

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“…In recent years, K. pneumoniae has emerged as a significant nosocomial and opportunistic pathogen. Antibiotic resistance, with the production of extended-spectrum β-lactamases (ESBL), carbapenemases or aminoglycosides resistance, is common in K. pneumoniae ( Raouf et al., 2022 ; Jwair et al., 2023 ; Khoshnood et al., 2023 ), which brings big challenges to the therapy of infection of K. pneumoniae . The emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has exhibited prevalence since 2010 ( Lan et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

Fang,

Dai,

Xiang

et al. 2023

Front. Cell. Infect. Microbiol.

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The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has driven us to explore alternative treatments for the limitation of antimicrobial agents. Lytic phages are considered a promising alternative treatment for CR-hvKP infection. In this study, we reported three novel lytic phages, vB_KpnA_SCNJ1-Z, vB_KpnS_SCNJ1-C, and vB_KpnM_SCNJ1-Y, against a CR-hvKP strain SCNJ1, and they possess genomes of double-stranded DNA with a size of 43,428 bp, 46,039 bp, and 50,360 bp, respectively. Phylogenetic analysis demonstrated that vB_KpnA_SCNJ1-Z belongs to the family Autographiviridae within the class Caudoviricetes, while vB_KpnS_SCNJ1-C and vB_KpnM_SCNJ1-Y are unclassified Caudoviricetes. The phages showed a narrow host range only lysing 1 of 50 tested clinical bacterial strains. The one-step growth curves and stability results showed that the phages displayed relatively short latency periods, with broad pH (pH 3-14) and thermal stabilities (20–60°C). The phages showed significant inhibition of the biofilm formation by SCNJ1 and strong antibacterial activity in vitro. In the mouse model, we demonstrated that administration of a single phage or phage cocktail significantly reduced bacteria loads in the lung, liver, and spleen, and effectively rescued mice from the infection of the SCNJ1 strain, with a survival rate of 70-80%. These findings suggested the three phages have great potential as an alternative therapy with favorable stability and strong antibacterial activity both in vivo and in vitro for the treatment of CR-hvKP infection.

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Section: Discussionmentioning

confidence: 99%

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

Fang,

Dai,

Xiang

et al. 2023

Front. Cell. Infect. Microbiol.

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“…DNA sequences of gyrA, gyrB , and parC were determined by the dideoxy chain termination method. 11 Furthermore, to compare the mRNA expression of the drug efflux pump gene acrA 12 , 13 between the parental strain and the strain exposed for 25 days, total RNA was extracted using TRI Reagent LS (Molecular Research Center, Inc., Cincinnati, OH). The mRNA expressions were quantified by the iTaq Universal CYBR Green One-step kit (BIO-RAD) and CFX Connect Real-Time System (BIO-RAD).…”

Section: Methodsmentioning

confidence: 99%

The Drug-Specific Propensity Regarding the Acquisition of Fluoroquinolone Resistance in Escherichia coli: An in vitro Challenge and DNA Mutation Analysis

Sato,

Ito,

Kawamura

et al. 2023

IDR

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Objective Many fluoroquinolones, such as ciprofloxacin, are used clinically. We investigated the relationship between resistance acquisition and exposure duration in each drug through the exposure of fluoroquinolone to Escherichia coli clinical isolates in vitro. Methods Eleven E. coli clinical isolates were exposed to each fluoroquinolone, ie, ciprofloxacin, levofloxacin, sitafloxacin, garenoxacin, and lascufloxacin, with the concentration of the mutant selection window for 5 days; these procedures were repeated 5-times. In addition, the DNA sequence in the quinolone-resistance determining region (QRDR) and the expression level in the drug efflux pump acrA were analyzed to determine the resistance mechanism. Results Although resistant strains were not detected after 5 to 10 days of exposure to fluoroquinolone, after 25 days of exposure to ciprofloxacin and levofloxacin, 100% and 45% of isolates acquired resistance, respectively. Due to 25 days of exposure to sitafloxacin, garenoxacin, and lascufloxacin, MIC measurement was elevated 2- to 4096-fold for those of the parental strain, and the cross-resistance rate to levofloxacin was 72%, 54%, and 27%, respectively. In strains with high fluoroquinolone resistance, acrA overexpression was observed in addition to QRDR mutation. Conclusion In our findings, fluoroquinolone resistance was not observed in the E. coli strain after 5- to 10-days of exposure. However, resistance acquisition was detected frequently after 15- to 25-days of exposure. Among fluoroquinolones, lascufloxacn had the least impact on the resistance acquisition in E. coli .

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“…Recently, it has been reported that there exists an inverse association between the existence of CRISPR/Cas system with antibiotic resistance, ESBL and carbapenemase production in antibiotic resistant bacteria, such as K. pneumonia . 73 In addition, the prevalence of CRISPR/Cas system and its possible association with antibiotic resistance has been reported in E. faecalis and E. faecium . 74 …”

Section: Crispr/cas System and Its Typesmentioning

confidence: 99%

Recent Advances in Understanding the Molecular Mechanisms of Multidrug Resistance and Novel Approaches of CRISPR/Cas9-Based Genome-Editing to Combat This Health Emergency

Allemailem

2024

IJN

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The rapid spread of multidrug resistance (MDR), due to abusive use of antibiotics has led to global health emergency, causing substantial morbidity and mortality. Bacteria attain MDR by different means such as antibiotic modification/degradation, target protection/modification/bypass, and enhanced efflux mechanisms. The classical approaches of counteracting MDR bacteria are expensive and time-consuming, thus, it is highly significant to understand the molecular mechanisms of this resistance to curb the problem from core level. The revolutionary approach of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated sequence 9 (CRISPR/Cas9), considered as a next-generation genome-editing tool presents an innovative opportunity to precisely target and edit bacterial genome to alter their MDR strategy. Different bacteria possessing antibiotic resistance genes such as mec A, erm B, ram R, tet A, mqr B and bla KPC that have been targeted by CRISPR/Cas9 to re-sensitize these pathogens against antibiotics, such as methicillin, erythromycin, tigecycline, colistin and carbapenem, respectively. The CRISPR/Cas9 from S. pyogenes is the most widely studied genome-editing tool, consisting of a Cas9 DNA endonuclease associated with tracrRNA and crRNA, which can be systematically coupled as sgRNA. The targeting strategies of CRISPR/Cas9 to bacterial cells is mediated through phage, plasmids, vesicles and nanoparticles. However, the targeting approaches of this genome-editing tool to specific bacteria is a challenging task and still remains at a very preliminary stage due to numerous obstacles awaiting to be solved. This review elaborates some recent updates about the molecular mechanisms of antibiotic resistance and the innovative role of CRISPR/Cas9 system in modulating these resistance mechanisms. Furthermore, the delivery approaches of this genome-editing system in bacterial cells are discussed. In addition, some challenges and future prospects are also described.

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Inverse Association between the Existence of CRISPR/Cas Systems with Antibiotic Resistance, Extended Spectrum β-Lactamase and Carbapenemase Production in Multidrug, Extensive Drug and Pandrug-Resistant Klebsiella pneumoniae

Cited by 18 publications

References 51 publications

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

The Drug-Specific Propensity Regarding the Acquisition of Fluoroquinolone Resistance in Escherichia coli: An in vitro Challenge and DNA Mutation Analysis

Recent Advances in Understanding the Molecular Mechanisms of Multidrug Resistance and Novel Approaches of CRISPR/Cas9-Based Genome-Editing to Combat This Health Emergency

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