Today is World Tuberculosis Day

Yet another year and a reminder that we need to work hard and work together to develop new measures to control and treat TB. On this day in 1882, Dr. Robert Koch declared that TB was caused by bacterium M. tuberculosis and demonstrated the pathogenesis of this disease. Today, 134 years after the discovery of the causative agent, we still do not have a firm control of this infectious agent. We need to work harder.
Click here to read statement released today by the World Health Organization regarding TB.

A little relief for recent earthquake victims in Nepal

In June we (six medical students from Lincoln-Memorial University, Tennessee, Dipendra, Matt et al, yours truly and my two brothers) made a trip to Sindhupalchowk and Kavrepalanchowk, Nepal, to help earthquake victims. We did medical camps and distributed supplies (medical, kids, expecting mother supplies...donated by friends and colleagues at Johns Hopkins University) and a lot of great meal bars donated by PRO-BAR. Click here for a link to see a blog by PRO-BAR. Health Concern Nepal also assisted us for travel logistics. Thank you everyone who supported. We did what little our small team could do.

The allies: Rifampicin and Carbapenems

Carbapenems and rifampicin exhibit synergistic activity against M. tuberculosis and M. abscessus in in vitro studies.  Click here.

LdtMt5 is a functionally and structurally distinct protein compared to LD-transpeptidase LdtMt2 of M. tuberculosis

Here is a paper from our group in which we describe how LdtMt5 is functionally and structurally different from LdtMt2, the dominant LD-transpeptidase in M. tuberculosis. Click here.

2015 WHO Tuberculosis Report

The World Health Organization recently published its Global TB Report_2015. One important declaration is that the burden of TB in humans (in terms of morbidity and mortality) appears to be higher than projected before. You can find the report here.
I think it will take a stronger determination to combat this disease. Let's work harder and together to tame this disease.

S. aureus Penicillin Binding Protein: allosteric binding site and modulation of catalytic site

This paper describes existence of an allosteric site that also binds to b-lactams and modulates the binding of second b-lactam molecule at the catalytic site. Click here.
Authors: J Fishovitz, N Taghizadeh, JF Fisher, M Chang, and S Mobashery.
Here are two additional papers from preceding this. Click here and here.

Peptidoglycan biosynthesis in Staphylococcus aureus

This paper demonstrates that many enzymes involved in biosynthesis peptidoglycan in S. aureus are dispensable (or redundant) for growth in stress free enriched media in vitro. But these enzymes mostly required under stress (from drug or from host). Click here.
Authors: P Reed, ML Atilano, R Alves, E Hoiczyk, X Sher, NT Reichmann, PM Pereira, T Roemer, SR Filipe, JB Pereira-leal, P Ligoxygakis, and MG Pinho.

Penicillin Binding Protein and PG of Pseudomonas aeruginosa

This paper describes involvement of a low molecular weight PBPs of P. aeruginosa in peptidoglycan metabolism and resistance to beta-lactams. Click here.
Authors: A Ropy, G Cabot, I Sanchez-Diener, C Aguilera, B Moya, JA Ayala, A Oliver.

Peptidoglycan and cell division in E. coli

This paper describes components of peptidoglycan coordinate with outer and inner membrane in E. coli during cell division. Click here.
Authors: AN Gray, AJ Egan, IL Vant Veer, J Verheul, A Colavin, A Koumoutsi, J Biboy, MA Altelaar, MJ Damen, KC Huang, JP Simorre, E Breukink, T den Blaauwen, A Typas, CA Gross, W Vollmer.

How do phages lyse bacterial cell wall?

This paper describes how lysis of (gram negative) bacterial cell wall by phages involves integrated targeting of the inner and outer membrane, their fusion and disruption of the peptidoglycan and the membranes. Click here.
Authors: M Rajaure, J Berry, R Kongari, J Cahill & R Young.

Peptidoglycan Remodeling in Corynebacterium glutamicum

This paper describes amidation of meso-diaminopimelic acid, catalyzed by LtsA, and resulting alteration of the peptidoglycan. Click here.
Authors: M Levefaudes, D Patin, C de Sousa-d'Auria, M Chami, D Blanot, M Herve, M Arthur, C Houssin and D Mengin-Lecreulx.

Tuberculosis Related Conferences & Meetings

Gordon Research Conference 2015: Tuberculosis Drug Discovery & Development
Keystone 2016: Tuberculosis Co-Morbidities & Immunopathogenesis
Enjoy the seminars, posters, discussions and creative ideas targeted at TB.

Meropenem and Clavulanic Acid

This paper describes clavulanic acid, as a companion, enhances activity of meropenem. Click here for this paper. John Blanchard's Lab has demonstrated this in M. tuberculosis.
Authors: J Cielecka-Piontek, D Szymanowska-Powalowska, M Paczkowska, P Lysakowski, P Zalewski and P Garbacki.

Here is another paper reporting Meropenem-Clavulanic acid activity against clinical strains (including strains that are resistant to TB drugs). Click here.
Authors: FL Davies  , CG Giske, J Bruchfeld, T Schon, P Jureen, K Anjeby.

Crystal Structure of MurU of Pseudomonas putida

This paper describes the molecular structure of MurU, an essential enzyme in the pathway for synthesis of peptidoglycan precursor. Click here.
Authors: M Renner-Schneck, I Hinderberger, J Gisin, T Exner, C Mayer, T Stehle

Antimicrobial Peptides and Inhibition of Peptidoglycan Biosynthesis

This paper probes inhibition of peptidoglycan biosynthesis using various inhibitors that act against targets and metabolites that comprise this pathway. Click here.
Authors: EB Breidenstein, P Courvalin, D Meziane-Cherif

Whole-cell NMR to Map Bacterial Peptidoglycan

In this work, scientists use highly sensitive tools to study bacterial peptidoglycan. Methods like these are instrumental to furthering our understanding of chemistry of the peptidoglycan. Click here.
Authors: R Nygaard, JA Romaniuk, DM Rice, L Cegelski

Drug Development for TB

This paper titled 'The future for early-stage tuberculosis drug discovery' reviews focuses on what is being done at the early stages of efforts to develop new drugs to treat TB. Click here.
Authors: ES Zuniga, J Early, T Parish

The Great Wall Symposium

A symposium centered on the peptidoglycan biology is a great idea as it bring this small but vital and active scientific community together. The organizers and supporters, Thank you.
Here is a very short description of the past symposium on peptidoglycan in Europe. Click here.
The next Great Wall Symposium is scheduled for September of this year. Click here.

Super (bad) Bugs on Regular New Media

Here is a news on CNN describing Super bugs in a hospital in Los Angeles. Click here.
There is a growing problem of bacterial pathogens that are resistant to exiting drugs. We have started a program title TREAT to address this national and global need for new antibiotics. Click here.
If you can help us sequence genomes of bacterial pathogens (to understand the genetic basis of mechanism of resistance) or have a chemical synthesis lab (to synthesize some molecules we have designed) please contact us at treat@jhu.edu
Together we can develop new antibiotics to treat these infections.

The Forgotten Plague: Tuberculosis

Here is the link to a documentary on the American history of Tuberculosis that was telecast recently by PBS. Click here.