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Synthetic Glycolipids and (p)ppGpp Analogs: Development of Inhibitors for Mycobacterial Growth, Biofilm and Stringent Response

  • Kirtimaan Syal
  • Krishnagopal Maiti
  • Kottari Naresh
  • Dipankar ChatterjiEmail author
  • N. JayaramanEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 842)

Abstract

Bacterial pathogens are the major cause of mortality across the globe, as current use of antibiotics and vaccines is unable to prevent the spread of bacterial pathogens. Rapid evolution allowed bacteria to overcome the hostile environmental conditions. Survival strategies, such as, biofilm formation, stringent response, sporulation, cyst formation and horizontal transfer of resistance genes have made it even more difficult to treat the bacterial disease. Rate of bacterial evolution has subdued the pace of discovery of new antibiotics. Most of the antibiotics target the lag and log phases of bacterial growth. It is realized that for complete omission of bacterial pathogens, survival strategies have to be restricted. Under stress, bacteria give rise to stringent response which initiates various signalling cascades escalating the activation of different survival strategies, including biofilm formation. Synthetic glycolipids and (p)ppGpp analogs hold promise to potential therapeutics for impeding the survival strategies. We have noticed earlier that various analogs of stringent response modulator (p)ppGpp hold promise for therapeutic intervention during stress. In addition, several small molecules, which are overproduced during biofilm formation, may also be targeted. In this article, such attempts are discussed.

Keywords

Biofilm Stringent response (p)ppGpp c-di-GMP GMP Glycolipids Mycobacteria Cell wall 

Abbreviations

(p)ppGpp

Guanosine 5′-(tri)diphosphate, 3′-diphosphate

c-di-GMP

Bis-(3′–5′)-cyclic dimeric guanosine monophosphate

CTD

C-terminal domain

DAP

Meso-2,6-diaminopimelic acid

EPS

Extracellular polymeric substance

GDP

Guanosine-5′-diphosphate

Gly

Glycine

GMP

Guanosine-5′-monophosphate

GPLs

Glycolipids

GTP

Guanosine-5′-triphosphate

KatG

Catalase-peroxidase

LAM

Lipoarabinomannan

LM

Lipomannan

mAGP

Mycolylarabinogalactan–peptidoglycan

PG

Peptidoglycan

PM

Plasma membrane

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Molecular Biophysics UnitIndian Institute of ScienceBangaloreIndia
  2. 2.Department of Organic ChemistryIndian Institute of ScienceBangaloreIndia

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