Benzalkonium tolerance genes and outcome in Listeria monocytogenes meningitis

1st Philip H.C. Kremer, 2nd John A. Lees, 3rd Merel M. Koopmans, 4th Bart Ferwerda, 5th Agaath W.M. Arends, 6th Monique M. Feller, 7th Kim Schipper, 8th Mercedes Valls Seron, 9th Arie van de Ende, 10th Matthijs C. Brouwer, 11th Diederik van de Beek and last Stephen D. Bentley


Objectives

Listeria monocytogenes is a foodborne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated listerial genetic variation and the relation with clinical outcome in meningitis.

Methods

We sequenced 96 isolates from adults with listerial meningitis included in two prospective nationwide cohort studies by whole genome sequencing, and evaluated associations between bacterial genetic variation and clinical outcome. We validated these results by screening listerial genotypes of 445 cerebrospinal fluid and blood isolates from patients over a 30-year period from the Dutch national surveillance cohort.

Results

We identified a bacteriophage, phiLMST6 co-occurring with a novel plasmid, pLMST6 in ST6 isolates to be associated with unfavourable outcome in patients (P=2.83e-05). The plasmid carries a benzalkonium chloride tolerance gene, emrC, conferring decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth inhibited at higher levels of benzalkonium chloride (median 60 mg/L versus 15 mg/L; P<0.001), and had higher minimum inhibitory concentrations for amoxicillin and gentamicin compared to isolates without emrC (both P<0.001). Transformation of pLMST6 into naïve strains led to benzalkonium chloride tolerance and higher minimum inhibitory concentrations for gentamicin.

Conclusions

These results show that a novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of ST6 listerial meningitis in The Netherlands. Suggesting increased disease severity, our findings warrant consideration of disinfectants used in food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome.

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