Whole-genome sequencing of the Mycobacterium tuberculosis Manila sublineage results in less clustering and better resolution than mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping.

Mycobacterium tuberculosis isolates of the Manila sublineage are genetically homogeneous. In this study, we used whole-genome sequencing (WGS) to type a collection of 36 M. tuberculosis isolates of the Manila family. WGS enabled the subtyping of these 36 isolates into at least 10 distinct clusters. Our results indicate that WGS is a powerful approach to determining the relatedness of Manila family M. tuberculosis isolates.

Identification and characterization of Cri1, a locus controlling mortality during Citrobacter rodentium infection in mice.

Infection of inbred mouse strains with Citrobacter rodentium represents an ideal model to reveal the genetic factors controlling host resistance to noninvasive enteric bacterial pathogens. We have chosen a positional cloning approach to identify putative gene(s) that control the known difference in survival between resistant C57BL/6J and susceptible C3H/HeJ and C3H/HeOuJ mice. Our work has identified one major locus within proximal chromosome 15 that is responsible for the marked susceptibility of both C3H strains, and we formally exclude Tlr4 from control of survival to this pathogen. We have named this new host resistance locus Cri1 (Citrobacter rodentium infection 1). The Cri1 genetic interval currently spans ∼16 Mb and it confers survival to the infection in a recessive manner. Transfer of the Cri1 locus from the surviving B6 mice into a congenic mouse with a C3Ou genetic background confirms its overall chromosomal localization and its highly significant effect on host survival. The C3Ou.B6-Cri1 mice thus produced have also enabled us to dissociate the control of mouse survival from the control of bacterial load early in the infection as well as from control of colonic hyperplasia.