Variation in Listeria monocytogenes dose responses in relation to subtypes encoding a full-length or truncated internalin A

Abstract

Internalin A (InlA; encoded by inlA) facilitates the crossing of the intestinal barrier by Listeria monocytogenes. Mutations leading to a premature stop codon (PMSC) in inlA and thus attenuated mammalian virulence have been reported. We recently characterized 502 L. monocytogenes food isolates from a retail survey and 507 human clinical isolates from multiple U.S. states with respect to the presence/absence of inlA mutations. The objective of this study was to investigate the hypothesis that dose responses for human listeriosis vary between L. monocytogenes strains with and those without a PMSC in inlA. Subtype-specific prevalence and concentration distributions in food, along with epidemiologic and consumption data, were input into established dose-response models to generate an r value (probability of a cell causing illness). Under the conservative assumption that L. monocytogenes levels at retail represent levels consumed, mean log(10) r values were -8.1 and -10.7 for L. monocytogenes subtypes with genes encoding a full-length and a truncated InlA, respectively. L. monocytogenes carrying a 5' frameshift mutation in a homopolymeric tract showed a mean log(10) r value of -12.1. Confidence intervals for the r values and their differences varied depending on subtypes. When the increase in concentration of L. monocytogenes subtypes between retail and consumption was considered, mean log(10) r values were reduced to -10.4, -13.8, and -12.8 for the subtypes with genes encoding a full-length InlA, for the subtypes carrying a PMSC in inlA, and for all L. monocytogenes isolates regardless of subtype, respectively. Our study provides further quantitative evidence that L. monocytogenes subtypes vary in abilities and relative likelihoods of causing human disease, which were mechanistically related to defined genetic markers.

FIG. 1.

Dose-response models for L. monocytogenes systemic infection derived from human and food epidemiological data and models derived from guinea pig experiments. Guinea pig results were from the work of Van Stelten (39). Results from the exponential model obtained from epidemiological data (⧫) in the study reported here are shown for the subgroup without inlA PMSCs (A) and for the subgroup with inlA PMSCs (B). For comparison, three models (beta-Poisson, log-logistic, and exponential) that provided acceptable fit to L. monocytogenes numbers recovered from infected guinea pigs are shown; guinea pig dose-response curves for an L. monocytogenes isolate encoding a full-length InlA (isolate CUFSL N1-054, H7550; obtained from a human case associated with the 1998-1999 listeriosis outbreak in the United States reported by the CDC [4]) are shown in panel A, while guinea pig dose-response curves for an L. monocytogenes isolate with an inlA PMSC (isolate CUFSL N1-040) are shown in panel B. The models derived from guinea pig data were represented in both panels by the following symbols: ▪, log-logistic; •, beta-Poisson; and ▴, exponential.