In:
Investigational Medicinal Chemistry and Pharmacology, Investigational Medicinal Chemistry and Pharmacology, Vol. 6, No. 2 ( 2023-12-31), p. 1-13
Abstract:
Background: Klebsiella has developed multiple-drug resistance (MDR) to a wide range of medicines, including carbapenems and third generation cephalosporins which are often regarded as the most effective drugs against MDR bacteria. The present study examined the anti-klebsiella, modes of action, and antibiotic-resistance reversal potential of Syzygium jambos (Myrtaceae) leaf (SJL) and bark (SJB) methanol extracts towards a panel of sixteen MDR K. pneumoniae and K. oxytoca strains and clinical isolates. Methods: The anti-klebsiella potential of SJL and SJB was assessed by determining the minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) using broth microdilution. Extracts were tested alone, in combination with an efflux pump inhibitor (PaβN), and in association with conventional antibiotics at their sub-inhibitory concentrations. Effects of SJL were also evaluated on bacterial kinetic growth, H+-ATPase-mediated pump, and cell membrane integrity, using standards. Results: SJL and SJB were shown to have anti-klebsiella action, with MICs ranging from 64 to 2048 g/mL. SJL was found to be more effective, acting on all tested pathogens with 100 ≤ MIC ≤ 2048 µg/mL, indicating considerable to moderate activity and generating bactericidal effects on more than half of the MDR Klebsiella strains investigated. SJL also produced a remarkably active effect (MIC ≤ 100 µg/mL), with MIC of 64 µg/mL against K. pneumoniae KP26. In the presence of PaβN, SJL and SJB activity rose significantly, demonstrating the involvement of active efflux machinery as MDR mechanisms. SJL displayed significant MDR reversal potential, as evidenced by an enhanced efficacy of conventional antibiotics, when in association. The activity of doxycycline and levofloxacin was improved on 100% of studied MDR pathogens. Interestingly, SJL also significantly enhanced the efficacy of the last resort drugs cefixime (cephalosporin) and imipenem (carbapenems) at more than 75% at MIC/2. Exposure of K. pneumoniae KP63 to SJL at 0.5×MIC, MIC, and 2×MIC for 20 h produced a concentration-dependent trend toward greater bacterial killing, extending the latent phase. In addition, SJL showed pronounced inhibition of the H+-ATPase-mediated pump and mildly disrupted the cytoplasmic membrane. Conclusion: This work provides a solid experimental foundation for considering S. jambos leaf extract as a viable treatment option for MDR Klebsiella-related illnesses. Keywords: Antibiotic-resistance modifying agents; efflux pump inhibitor; food plants; Klebsiella infections; multidrug resistance; Syzygium jambos.
Type of Medium:
Online Resource
ISSN:
2617-0019
,
2617-0027
DOI:
10.31183/imcp.2023.v6i2
DOI:
10.31183/imcp.2018.xxxxx
DOI:
10.31183/imcp.2023.00082
Language:
Unknown
Publisher:
Investigational Medicinal Chemistry and Pharmacology
Publication Date:
2023
