Multidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission. We did a population-based, retrospective study of patients who tested positive for tuberculosis between Jan 1, 2009, and Dec 31, 2012, in Shanghai, China. We did variable-number-of-tandem-repeat genotyping and whole-genome sequencing of isolates. We measured strain diversity within and between genomically clustered isolates. Genomic and epidemiological data were combined to construct transmission networks. 367 (5%) of 7982 patients with tuberculosis had MDR tuberculosis and 324 (88%) of these had isolates available for genomic analysis. 103 (32%) of the 324 MDR strains were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission of MDR strains. Patients who had delayed diagnosis or were older than 45 years had high risk of recent transmission. 235 (73%) patients with MDR tuberculosis probably had transmission of MDR strains. Transmission network analysis showed that 33 (87%) of the 38 clusters accumulated additional drug-resistance mutations through emergence or fixation of mutations during transmission. 68 (66%) of 103 clustered MDR strains had compensatory mutations of rifampicin resistance. Recent transmission of MDR tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis. National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

Significance: Mycobacterium tuberculosis Beijing family is a group of globally emerging bacterial strains that are responsible for more than a quarter of the global tuberculosis epidemic. Here, we combine whole-genome sequencing and large-scale genotyping to map the temporal and spatial changes of the genetic diversity within this strain family. We reveal a southern East Asia origin and a parallel evolution of this bacterial genotype with modern humans in East Asia during the last 30,000 years. The recently globally emerged Beijing strains mainly belong to a hypervirulent subtype that most likely has initially been selected for adaption to increased population densities during the agricultural transition in northern China.

Background. Drug-resistant tuberculosis poses a growing challenge to global public health. However, the diversity and dynamics of the bacterial population during acquisition of drug resistance have yet to be carefully examined. Methods. Whole-genome sequencing was performed on 7 serial Mycobacterium tuberculosis (M. tuberculosis) populations from 3 patients during different stages in the development of drug resistance. The population diversity was assessed by the number and frequencies of unfixed mutations in each sample. Results. For each bacterial population, 8–41 unfixed mutations were monitored by the fraction of single-nucleotide polymorphisms at specific loci. Among them, as many as 4 to 5 resistance-conferring mutations were transiently detected in the same single sputum, but ultimately only a single type of mutant was fixed. In addition, we identified 14 potential compensatory mutations that occurred during or after the emergence of resistance-conferring mutations. Conclusions. M. tuberculosis population within patients exhibited considerable genetic diversity, which underwent selections for most fit resistant mutant. These findings have important implications and emphasize the need for early diagnosis of tuberculosis to decrease the chance of evolving highly fit drug-resistant strains.

Background Staphylococcus epidermidis is a common cause of nosocomial infections worldwide. This study analyzed the differences in genetic endowment and clonal lineages with pathogenesis and resistance traits of S. epidermidis isolates collected from community and hospital environments (patients and healthcare staff) of the same ecological niche, time period, and geographical location in China. Methodology/Principal Findings Molecular epidemiology and population analysis showed that nasal colonization rates of S. epidermidis in the community of Shanghai area of China and in healthcare personnel were 44.8% (methicillin-resistant S. epidermidis , MRSE: 17.2%) and 61.3% (MRSE: 30.0%), respectively. 86.7% of clinical isolates were MRSE. Among the strains studied, 44 sequence types (STs) were identified with 91.7% belonging to clonal complex 2 (CC2). Only 40.8% isolates from patients were also found in healthy individuals. MRSE-ST2-SCC mec III was the predominant clone in clinical isolates, almost resistant to all antibiotics tested. Biofilm-related genes IS256 and icaA were detected in majority of the predominant clinical MRSE-ST2 clone with a 40.5% biofilm-positive rate. No ST2 isolate was found in community setting. We found a high prevalence of arginine catabolic mobile element (ACME) (74.1%). The prevalence of ACME- arc and ACME- opp3 clusters was 71.6% and 32.4%, respectively. Methicillin-sensitive S. epidermidis (MSSE) isolates harbored more ACME (83.3%) than MRSE isolates (67.7%), and there was no association between ACME and SCC mec types. An association was found between low-level ACME presence and invasive infections. Conclusions/Significance We observed a high level of diversity within S. epidermidis in this study, with CC2 as the dominant clonal complex in both community and hospital settings. Only 40.8% of the isolates from patients were also found in healthy individuals. Contrary to that biofilm formation and multiple antibiotic resistance were associated closely with pathogenicity of S. epidermidis , ACME was more likely to be an indicator for colonization rather than a virulence factor.