Abstract
ABSTRACT
The emergence of plasmid-mediated colistin resistance in Shiga toxin-producing
Escherichia coli
(STEC) is an important public health concern because these strains can combine antimicrobial resistance with intestinal pathogenic potential. However, although
mcr
-harboring STEC has been reported from food-related sources, the phenotypic consequences of
mcr-1
acquisition in STEC remain poorly understood. In this study, we investigated the prevalence of
mcr
variants and associated antimicrobial resistance determinants among 144
mcr
-harboring STEC isolates and examined the phenotypic impact of
mcr-1
in
E. coli
O157:H7 ATCC 43894. Among the
mcr
-harboring STEC isolates,
mcr-1
was the predominant
mcr
variant (63.9%), and 88.9% of
mcr-1
-positive isolates were multidrug-resistant. Notably, genomically predicted fosfomycin resistance determinants were detected in 84.8% of
mcr-1
-positive isolates. Acquisition of the
mcr-1
-harboring plasmid in
E. coli
O157:H7 ATCC 43894 increased adhesion to HEp-2 epithelial cells but reduced swimming motility, biofilm formation, and
Galleria mellonella
mortality. The reduced
G. mellonella
mortality may reflect altered innate immune stimulation. These changes were accompanied by remodeling of the lipopolysaccharide profile, with reduced banding in both the O-antigen and core-lipid A regions, reduced endotoxin levels, increased cell surface hydrophobicity, a less negative zeta potential, and reduced autoagglutination, all of which were
mcr-1
-dependent in knockout and complementation experiments. Collectively, these findings indicate that
mcr-1
contributes beyond colistin resistance, converging on a coordinated reshaping of cell surface architecture and host interaction together with co-selection of resistance to other clinically relevant antibiotics, including fosfomycin.
IMPORTANCE
Shiga toxin-producing
Escherichia coli
is a major foodborne pathogen, but treatment options are limited because some antibiotics increase the risk of severe disease. Mobile colistin resistance genes in this pathogen are therefore concerning, especially alongside resistance to other clinically relevant antibiotics. This study shows that
mcr-1
is the predominant colistin resistance gene among
mcr
-harboring Shiga toxin-producing
E. coli
and that these isolates frequently carry multidrug resistance determinants, including fosfomycin resistance. We further show that
mcr-1
acquisition reshapes the bacterial cell surface and alters host-associated phenotypes in
E. coli
O157. Despite reduced mortality in
Galleria mellonella
, increased epithelial cell adhesion suggests that the reduced mortality may reflect altered innate immune stimulation rather than an overall attenuation of host-colonization potential. These findings suggest that
mcr-1
is not only a colistin resistance determinant but also a factor associated with broader changes in resistance, surface architecture, and host interaction in foodborne
E. coli
.