Efficacy of carvacrol against resistant rapidly growing mycobacteria in the planktonic and biofilm growth mode.

Emanuela Marini,Luigina Cellini,Antonia Nostro,Mara Di Giulio,Giovanna Ginestra,Gloria Magi,Bruna Facinelli,Silvia Di Lodovico,Andreana Marino,Olivier Habimana

doi:10.1371/journal.pone.0219038

Abstract

Rapidly growing mycobacteria (RGM) are environmental bacteria found worldwide with a propensity to produce skin and soft-tissue infections. Among them, the most clinically relevant species is Mycobacterium abscessus. Multiple resistance to antibiotics and the ability to form biofilm contributes considerably to the treatment failure. The search of novel anti-mycobacterial agents for the control of biofilm growth mode is crucial. The aim of the present study was to evaluate the activity of carvacrol (CAR) against planktonic and biofilm cells of resistant RGM strains. The susceptibility of RGM strains (n = 11) to antibiotics and CAR was assessed by MIC/MBC evaluation. The CAR activity was estimated by also vapour contact assay. The effect on biofilm formation and preformed biofilm was measured by evaluation of bacterial growth, biofilm biomass and biofilm metabolic activity. MIC values were equal to 64 μg/mL for most of RGM isolates (32–512 μg/mL), MBCs were 2–4 times higher than MICs, and MICs of vapours were lower (16 μg/mL for most RGM isolates) than MICs in liquid phase. Regarding the biofilm, CAR at concentrations of 1/2 × MIC and 1/4 × MIC showed a strong inhibition of biofilm formation (61–77%) and at concentration above the MIC (2–8 × MIC) produced significant inhibition of 4- and 8-day preformed biofilms. In conclusion, CAR could have a potential use, also in vapour phase, for the control of RGM.

Highlights

Growing mycobacteria (RGM) are environmental bacteria capable of causing a wide spectrum of infections [1]
Growing mycobacteria strains were identified as smooth morphotypes M. abscessus #09716, #29904, #30235, #70513, #73596, #90459, #74600; M. chelonae #74471; M. fortuitum #26647; M. mucogenicum #45646 and M. smegmatis #44041 by line-probe reverse hybridization assay (GenoType CM, Hain Lifescience, Nehren, Germany) and conventional biochemical and cultural methods, as suggested by Clinical and Laboratory Standard Institute (CLSI) [27]
Susceptibility of Rapidly growing mycobacteria (RGM) strains to antibiotics and CAR

Summary

Introduction

Growing mycobacteria (RGM) are environmental bacteria capable of causing a wide spectrum of infections [1]. Mycobacterium abscessus is an emerging human pathogen causing lung infection and responsible for wound, catheter and eye infections and tattooing [2]. Mycobacterium chelonae is commonly associated with skin and soft tissue infections and causes catheter-related and post-surgical infections; invasive infections are common in immunosuppressed patients but pulmonary infections are rare when. Carvacrol activity on rapidly growing mycobacteria compared to M. abscessus [3]. Mycobacterium fortuitum is responsible for the most of post-surgical wound and catheter infections produced by the RGM [4]. Mycobacterium mucogenicum causes osteomyelitis and respiratory tract, bloodstream and disseminated infections in both immunocompetent and immunocompromised hosts [4]

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