S22: Aldehyde Resistance: What the Latest Studies in Mycobacteria are Telling Us

Non-tuberculous Mycobacterium spp. (NTM) are ubiquitous in the environment and cause infections and pseudo-infections in health care settings throughout the world. Of particular concern is the increasing frequency with which glutaraldehyde-resistant Mycobacterium abscessus (subsp. abscessus and subsp. massiliense) and Mycobacterium chelonae are being associated with nosocomial outbreaks, sometime reaching epidemic proportions as recently documented in Brazil. Glutaraldehyde (GTA) is the most widely used chemical disinfectant for heat-sensitive medical devices in hospitals worldwide.

What is known of the mode of action of this disinfectant in other microorganisms suggests that changes in the surface-exposed composition of the cell envelope resulting in decreased binding and/or penetration of GTA may be one of the mechanisms through which NTM develop high levels of resistance. Because of the important role played by the mycobacterial outer membrane in drug susceptibility and host-pathogen interactions, there is thus some concern that the widespread use of GTA and other related aldehyde disinfectants in clinical settings is impacting on the selection of resistant populations of NTM with possible consequences on cross-resistance to drugs and pathogenicity. In support of this assumption, we recently demonstrated that reduced porin expression was one of the mechanisms through which M. smegmatis and M. chelonae develop high levels of resistance to GTA and a further aldehyde disinfectant, ortho-phthalaldehyde (OPA). In part due to defects in porin expression, the GTA/OPA-resistant M. chelonae isolate under study also displayed unusually high levels of resistance to a number of drugs including rifampicin, ciprofloxacin, clarithromycin, erythromycin, vancomycin, tetracycline and linezolid, and increased pathogenicity in amoebae.