Recombinant M. Tuberculosis MTC28 Protein

To estimate the incidence of pulmonary tuberculosis (PTB) in Chinese diabetes patients and to evaluate the effect of blood glucose on PTB risk, a retrospective cohort study was built based on the diabetes management system in Shanghai and included 240,692 adults aged 35 or above. Incidences of PTB in all diabetes patients and by subgroups were calculated and compared. Multivariable Cox regression models with restricted cubic splines were used to evaluate the association of fasting plasma glucose (FPG) with the risk of PTB. A total of 439 incident PTB cases were identified in the cohort after an average of 3.83 years of follow-up. The overall PTB incidence rate was 51.3/100,000 in diabetes patients, and annual incidence remained higher than that in general population. The PTB incidence rate of diabetes patients was higher in men than in women (86.2 vs. 22.1 per 100,000) and was highest in patients with body mass index (BMI)<18.5kg/m(2) (215.2/100,000) or FPG10mmol/L (143.2/100,000). Our results suggest that the risk of tuberculosis may be greater at higher levels of FPG in diabetes patients of normal weight. Specific tuberculosis screening strategies for different characteristic diabetes population should be provided to prevent and control tuberculosis in China.

Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains are spreading globally, and thus, new antituberculosis drugs are urgently needed. The M tuberculosis L,D-transpeptidase LdtMt2 is directly involved in peptidoglycan formation, bacterial virulence and plactam resistance. This enzyme is a potential antituberculosis target that can be inhibited by carbapenems, FDA-approved drugs that are used in the treatment of tuberculosis. Two different intermediate states, states I and II, have been reported for LdtMt2 interacting with carbapenems, such as ertapenem, imipenem and meropenem. State I was proposed as an initial adduct formation state, whereas state II was proposed as a stable protein-ligand interaction state accompanied by local conformational arrangements of both carbapenem and the protein. Here, we report a new LdMt2-ertapenem interaction state, I-plus, with the same carbapenem conformation as state II and a similar local protein conformation to state I. This new state was proposed as an intermediate state for the transition from state I to state II, in which the ertapenem molecule, but not the protein, undergoes a conformational change. Our work helps elucidate the changes that occur after carbapenem acts on LdtMt2 and, together with the other reported state, demonstrates how the L,D-transpeptidase interacts with carbapenems.