Molecular mechanisms of disinfectant resistance in Klebsiella pneumoniae

Abstract

Objectives: chemical disinfectants are critical for infection control in healthcare environments and beyond, as exemplified by their vital role during the COVID-19 pandemic. Despite research repeatedly demonstrating that bacteria can develop adaptations that mitigate the efficacy of chemical disinfectants, the underlying molecular mechanisms remain poorly characterized. This study investigates the mechanisms that underpin resistance demonstrated by disinfectant-adapted Klebsiella pneumoniae NCTC 13443 samples.

Methods: resistant samples have previously undergone long-term in vitro adaptation via serial passage in increasing concentrations of common disinfectants benzalkonium chloride (BAC), didecydimethylammonium chloride (DDAC), polyhexamethylene biguanide (PHMB), chlorocresol or bronopol. A multi-omics approach was used to conduct in-depth molecular analyses of the adaptations that contribute to resistance.

Results: K. pneumoniae adaptation to BAC, DDAC and PHMB was associated with the modification of lipid A causing the reduction of the net-negative charge of the outer surface, lowering the affinity of cationic disinfectants. This mechanism is also used for polymyxin and colistin resistance, highlighting a potential cross-resistance risk. Chlorocresol-adapted K. pneumoniae samples demonstrated increased expression of efflux pumps and expression changes linked to biofilm formation. Bronopol resistance was associated with promoting biofilm formation and increased thioredoxin expression to alleviate oxidative stress. Results indicate the potential role of N-ethylmaleimide reductase NemA in bronopol resistance via enzymatic degradation.

Conclusions: these findings provide novel insights into how causative pathogens of healthcare-associated infections can adapt to and mitigate the effectiveness of common chemical disinfectants that are relied on globally every day as a critical infection control measure.

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Identifiers

ORCID for Daniel J. Noel: orcid.org/0000-0001-8560-4441

ORCID for Alistair Bailey: orcid.org/0000-0003-0023-8679

ORCID for Benjamin I. Nicholas: orcid.org/0000-0003-1467-9643

ORCID for Paul Skipp: orcid.org/0000-0002-2995-2959

ORCID for C. William Keevil: orcid.org/0000-0003-1917-7706

ORCID for Sandra A. Wilks: orcid.org/0000-0002-4134-9415

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