Pathogenic Escherichia coli strains cause a wide variety of intestinal and extraintestinal infections. The widespread geographical clonal dissemination of intestinal pathogenic E. coli strains, such as E. coli O157:H7, is well recognized, and its spread is most often attributed to contaminated food products. On the other hand, the clonal dissemination of extraintestinal pathogenic E. coli (ExPEC) strains is also recognized, but the mechanism of their spread is not well explained. Here, I describe major pandemic clonal lineages of ExPEC based on multilocus sequence typing (MLST), and discuss possible reasons for their global dissemination. These lineages include sequence type (ST)131, ST393, ST69, ST95, and ST73, which are all associated with both community-onset and healthcare-associated infections, in particular urinary tract infections and bloodstream infections. As with many other types of drug-resistant Gram-negative and Gram-positive bacterial infections, drug-resistant ExPEC infections are recognized to be caused by a limited set of clonal lineages. However, reported observations on these major pandemic lineages suggest that the resistance phenotype is not necessarily the determinant of their clonal dissemination. Both epidemiological factors and their intrinsic biological 'fitness' are likely to contribute. An important public health and clinical concern is that pandemicity itself may be a determinant of progressive drug resistance acquisition by clonal lineages. New research is urgently needed to better understand the epidemiological and biological causes of ExPEC pandemicity.

The genome of Mycobacterium tuberculosis harbors four copies of a cluster of genes termed mce operons. Despite extensive research that has demonstrated the importance of these operons on infection outcome, their physiological function remains obscure. Expanding databases of complete microbial genome sequences facilitate a comparative genomic approach that can provide valuable insight into the role of uncharacterized proteins. The M. tuberculosis mce loci each include two yrbE and six mce genes, which have homology to ABC transporter permeases and substrate-binding proteins, respectively. Operons with an identical structure were identified in all Mycobacterium species examined, as well as in five other Actinomycetales genera. Some of the Actinomycetales mce operons include an mkl gene, which encodes an ATPase resembling those of ABC uptake transporters. The phylogenetic profile of Mkl orthologs exactly matched that of the Mce and YrbE proteins. Through topology and motif analyses of YrbE homologs, we identified a region within the penultimate cytoplasmic loop that may serve as the site of interaction with the putative cognate Mkl ATPase. Homologs of the exported proteins encoded adjacent to the M. tuberculosis mce operons were detected in a conserved chromosomal location downstream of the majority of Actinomycetales operons. Operons containing linked mkl, yrbE and mce genes, resembling the classic organization of an ABC importer, were found to be common in Gram-negative bacteria and appear to be associated with changes in properties of the cell surface. Evidence presented suggests that the mce operons of Actinomycetales species and related operons in Gram-negative bacteria encode a subfamily of ABC uptake transporters with a possible role in remodeling the cell envelope.

Although many strain typing methods exist for pathogenic Escherichia coli , most have drawbacks in terms of resolving power, interpretability, or scalability. For this reason, multilocus sequence typing (MLST) is an appealing alternative. However, its applicability to different pathogens in specific epidemiologic contexts is not well understood. Here, we applied a previously established MLST method based on housekeeping genes to a well-characterized collection of uropathogenic E. coli isolates to compare the discriminatory ability of this procedure with that of enterobacterial repeat intergenic consensus (ERIC2) PCR, serogrouping, and pulsed-field gel electrophoresis (PFGE). Among 45 E. coli isolates studied, 17 different multilocus sequence types (ST) were identified. One MLST group (designated ST69 complex) was comprised of 22 isolates, all belonging to uropathogenic and bacteremic E. coli strains previously defined as clonal group A (CgA) by ERIC2 PCR. The ST69 strains contained five different serogroups and 14 PFGE types. ERIC2 PCR CgA strains belonging to different MLST groups were also identified. Interestingly, one cow E. coli isolate, previously shown by PFGE to be closely related to a human uropathogenic CgA strain, was found to cluster with the ST69 strains. All of the other animal and environmental CgA isolates had different MLST profiles. The discriminatory power of this MLST method based on housekeeping genes appears to be higher than that of ERIC2 PCR but lower than that of PFGE for epidemiologic study of uropathogenic E. coli .

Urban slums, like refugee communities, comprise a social cluster that engenders a distinct set of health problems. With 1 billion people currently estimated to live in such communities, this neglected population has become a major reservoir for a wide spectrum of health conditions that the formal health sector must deal with. Unlike what occurs with refugee populations, the formal health sector becomes aware of the health problems of slum populations relatively late in the course of their illnesses. As such, the formal health sector inevitably deals with the severe and end-stage complications of these diseases at a substantially greater cost than what it costs to manage non-slum community populations. Because of the informal nature of slum settlements, and cultural, social, and behavioral factors unique to the slum populations, little is known about the spectrum, burden, and determinants of illnesses in these communities that give rise to these complications, especially of those diseases that are chronic but preventable. In this article, we discuss observations made in one slum community of 58,000 people in Salvador, the third largest city in Brazil, to highlight the existence of a spectrum and burden of chronic illnesses not likely to be detected by the formal sector health services until they result in complications or death. Lack of health-related data from slums could lead to inappropriate and unrealistic allocation of health care resources by the public and private providers. Similar misassumptions and misallocations are likely to exist in other nations with large urban slum populations. Continued neglect of ever-expanding urban slum populations in the world could inevitably lead to greater expenditure and diversion of health care resources to the management of end-stage complications of diseases that are preventable. A new approach to health assessment and characterization of social-cluster determinants of health in urban slums is urgently needed.

Escherichia coliis one of the most well-adapted and pathogenically versatile bacterial organisms. It causes a variety of human infections, including gastrointestinal illnesses and extraintestinal infections. It is also part of the intestinal commensal flora of humans and other mammals. Groups ofE. colithat cause diarrhea are often described as intestinal pathogenicE. coli(IPEC), while those that cause infections outside of the gut are called extraintestinal pathogenicE. coli(ExPEC). IPEC can cause a variety of diarrheal illnesses as well as extraintestinal syndromes such as hemolytic-uremic syndrome. ExPEC cause urinary tract infections, bloodstream infection, sepsis, and neonatal meningitis. IPEC and ExPEC have thus come to be referred to as pathogenic variants ofE. colior pathovars. While IPEC can be distinguished from commensalE. colibased on their characteristic virulence factors responsible for their associated clinical manifestations, ExPEC cannot be so easily distinguished. IPEC most likely have reservoirs outside of the human intestine but it is unclear if ExPEC represent nothing more than commensalE. colithat breach a sterile barrier to cause extraintestinal infections. This question has become more complicated by the advent of whole genome sequencing (WGS) that has raised a new question about the taxonomic characterization ofE. colibased on traditional clinical microbiologic and phylogenetic methods. This review discusses how molecular epidemiologic approaches have been used to address these questions, and how answers to these questions may contribute to our better understanding of the epidemiology of infections caused byE. coli. *This article is part of a curated collection.

Background: More than 200 studies related to nucleic acid amplification (NAA) tests to detect Mycobacterium tuberculosis directly from clinical specimens have appeared in the world literature since this technology was first introduced. NAA tests come as either commercial kits or as tests designed by the reporting investigators themselves (in-house tests). In-house tests vary widely in their accuracy, and factors that contribute to heterogeneity in test accuracy are not well characterized. Here, we used meta-analytical methods, including meta-regression, to identify factors related to study design and assay protocols that affect test accuracy in order to identify those factors associated with high estimates of accuracy. Results: By searching multiple databases and sources, we identified 2520 potentially relevant citations, and analyzed 84 separate studies from 65 publications that dealt with in-house NAA tests to detect M. tuberculosis in sputum samples. Sources of heterogeneity in test accuracy estimates were determined by subgroup and meta-regression analyses. Among 84 studies analyzed, the sensitivity and specificity estimates varied widely; sensitivity varied from 9.4% to 100%, and specificity estimates ranged from 5.6% to 100%. In the meta-regression analysis, the use of IS6110 as a target, and the use of nested PCR methods appeared to be significantly associated with higher diagnostic accuracy. Conclusion: Estimates of accuracy of in-house NAA tests for tuberculosis are highly heterogeneous. The use of IS6110 as an amplification target, and the use of nested PCR methods appeared to be associated with higher diagnostic accuracy. However, the substantial heterogeneity in both sensitivity and specificity of the in-house NAA tests rendered clinically useful estimates of test accuracy difficult. Future development of NAA-based tests to detect M. tuberculosis from sputum specimens should take into consideration these findings in improving accuracy of in-house NAA tests.