In vitro activity of human defensins HNP-1 and hBD-3 against multidrug-resistant ESKAPE Gram-negatives of clinical origin and selected peptidoglycan recycling-defective mutants

被引：0

作者：

Escobar-Salom, Maria ^{[1
,2
,3
]}

Barcelo, Isabel Maria ^{[1
,2
,3
]}

Rojo-Molinero, Estrella ^{[1
,2
,3
]}

Jordana-Lluch, Elena ^{[1
,2
,3
]}

Cabot, Gabriel ^{[1
,2
,3
]}

Oliver, Antonio ^{[1
,2
,3
]}

Juan, Carlos ^{[1
,2
,3
]}

机构：

[1] Univ Hosp Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Palma De Mallorca, Spain

[2] Univ Hosp Son Espases, Microbiol Dept, Palma De Mallorca, Spain

[3] Ctr Invest Biomed Red Enfermedades Infecciosas CIB, Madrid, Spain

来源：

MICROBIOLOGY SPECTRUM | 2024年 / 12卷 / 04期

关键词：

ESKAPE Gram-negatives; Pseudomonas aeruginosa; Klebsiella pneumoniae; Enterobacter cloacae complex; Acinetobacter baumannii; Human Neutrophil Peptide-1 (HNP-1); human Beta Defensin 3 (hBD-3); peptidoglycan recycling; HUMAN BETA-DEFENSINS; CAPSULE POLYSACCHARIDE; ANTIMICROBIAL PEPTIDES; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC ACTIVITIES; HUMAN BETA-DEFENSIN-3; BACTERIA; EXPRESSION; ANALOGS;

D O I：

10.1128/spectrum.00358-24

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The use of immune compounds as antimicrobial adjuvants is a classic idea recovering timeliness in the current antibiotic resistance scenario. However, the activity of certain antimicrobial peptides against ESKAPE Gram-negatives has not been sufficiently investigated. The objective of this study was to determine the activities of human defensins HNP-1 and hBD-3 alone or combined with permeabilizing/peptidoglycan-targeting agents against clinical ESKAPE Gram-negatives [Acinetobacter baumannii (AB), Enterobacter cloacae (EC), Klebsiella pneumoniae (KP), and acute/chronic Pseudomonas aeruginosa (PA)]. Lethal concentrations (LCs) of HNP-1 and hBD-3 were determined in four collections of multidrug resistant EC, AB, KP, and PA clinical strains (10-36 isolates depending on the collection). These defensins act through membrane permeabilization plus peptidoglycan building blockade, enabling that alterations in peptidoglycan recycling may increase their activity, which is why different recycling-defective mutants were also included. Combinations with physiological lysozyme and subinhibitory colistin for bactericidal activities determination, and with meropenem for minimum inhibitory concentrations (MICs), were also assessed. HNP-1 showed undetectable activity (LC > 32 mg/L for all strains). hBD-3 showed appreciable activities: LC ranges 2-16, 8-8, 8->32, and 8->32 mg/L for AB, EC, KP, and PA, being PA strains from cystic fibrosis significantly more resistant than acute origin ones. None of the peptidoglycan recycling-defective mutants showed greater susceptibility to HNP-1/hBD-3. Combination with colistin or lysozyme did not change their bactericidal power, and virtually neither did meropenem + hBD-3 compared to meropenem MICs. This is the first study comparatively analyzing the HNP-1/hBD-3 activities against the ESKAPE Gram-negatives, and demonstrates interesting bactericidal capacities of hBD-3 mostly against AB and EC.

引用

页数：15