Cluster-dependent colistin hetero-resistance in Enterobacter cloacae complex

Area of Science:

• Microbiology
• Genetics
• Antimicrobial Resistance

Background:

• The Enterobacter cloacae complex (ECC) is a significant nosocomial pathogen.
• Colistin is a crucial last-resort antibiotic for treating multidrug-resistant Gram-negative infections.
• Understanding colistin hetero-resistance mechanisms in ECC is vital for effective treatment strategies.

Purpose of the Study:

• To investigate the influence of cluster membership on colistin hetero-resistance in ECC.
• To elucidate the genetic underpinnings of colistin hetero-resistance within the ECC.

Main Methods:

• Phenotypic analysis of colistin hetero-resistance using broth microdilution, Etest, and population analysis profiling.
• Genetic analysis involving the construction and testing of various mutants (e.g., ΔphoP, ΔphoQ, ΔpmrA) for hetero-resistance.

Main Results:

• Colistin hetero-resistance in ECC was found to be cluster-dependent, with specific clusters exhibiting higher rates.
• Population analysis revealed a small resistant subpopulation in some susceptible strains.
• The arn operon and the PhoP/PhoQ two-component regulatory system were identified as key mechanisms driving hetero-resistance.

Conclusions:

• Cluster identification of ECC strains should be performed alongside colistin MIC testing due to the observed cluster-dependent hetero-resistance.
• The resistance mechanism in ECC appears distinct from other Enterobacteriaceae, primarily involving the PhoP/PhoQ system rather than PmrA/PmrB.