alexa Drug-Tolerant Mycobacteria: Are Biofilms or Signaling Mechanisms Controlling its Production an Option to Find New Drugs? | Open Access Journals
ISSN: 2161-1068
Mycobacterial Diseases
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Drug-Tolerant Mycobacteria: Are Biofilms or Signaling Mechanisms Controlling its Production an Option to Find New Drugs?

Perla Jazmín Vega-Domínguez and Mario Alberto Flores-Valdez*

Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C., Unidad de Biotecnología Médica y Farmacéutica, México

Corresponding Author:
Mario Alberto Flores-Valdez
Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco
A.C., Unidad de Biotecnología Médica y Farmacéutica, México
E-mail: [email protected]

Received Date: October 10, 2013; Accepted Date: October 11, 2013; Published Date: October 18, 2013

Citation: Vega-Domínguez PJ, Flores-Valdez MA (2013) Drug-Tolerant Mycobacteria: Are Biofilms or Signaling Mechanisms Controlling its Production an Option to Find New Drugs? Mycobact Diseases 3:e121. doi:10.4172/2161-1068.1000e121

Copyright: © 2013 Vega-Domínguez PJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Mycobacterial Diseases

Human tuberculosis (TB) is a reemerging disease caused mainly by bacilli of the Mycobacterium tuberculosis (Mtb) complex. In its 2012 Global Tuberculosis Report, the World Health Organization (WHO) estimated 1.4 million deaths in 2011 due to this disease, and almost one million of these deaths were among HIV patients. Also, 6.8 new million cases were notified, and WHO estimates that 19% correspond to multidrug resistant TB (MDR TB), this is TB resistant to isoniazid (INH) and rifampicin (Rif), the two principal drugs used for TB treatment.

Chemotherapy of drug-susceptible TB requires a long period of time: the first phase lasts about 2 months, and the second one from 4 to 7 more months. This period becomes longer when treating MDR TB. This prolonged regime is thought to be required given that TB patients might contain bacilli distributed among heterogeneous populations: those that are actively replicating (and fully susceptible to first-line drugs) and those that sporadically replicate and become persistent. In order to reduce the duration of the treatment is necessary to study the physiology of persistent bacilli.

Recently, Ojha et al. proposed a new approach to study this persistent population: biofilms [1]. Biofilms are communities of microorganisms immersed into a matrix formed by secreted polymers such as polysaccharides, lipids or nucleic acids. This phenotype has been extensively studied in pathogens capable of causing persistent infections and it has been noted also that a microorganisms within biofilm are more tolerant to antibiotic than the same microorganisms grown planktonically [2]. When screening for molecules against biofilm formation in M. smegmatis, Wang and cols. found that one of their tested molecules, named TCA1, was able to inhibit production of biofilm by Mtb, and showed bactericidal activity in vitro, and in both an acute and a chronic infection mice model [3], therefore indicating that screening for biofilms inhibitors might lead to discover or rationally design new anti-TB drugs.

In many microorganisms biofilm formation is triggered by high concentrations of the second messenger bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) where synthesis and degradation occur by the action of the diguanylate cylases (DGC) and phosphodiesterases (PDE), respectively [4]. Mtb H37Rv spontaneously forms biofilm in vitro when cultured on detergent free media and possess genes (Rv1354c and Rv1357c) whose products are respectively responsible for synthesizing and degrading c-di-GMP in vitro.

A recent study suggests that c-di-GMP regulate dormancy and virulence in Mtb H37Rv, by a mechanism independent of the transcriptional regulator DosR [5]. There, an Mtb H37Rv strain lacking Rv1357c, the gene that codes for the PDE in this strain, was less able than wild type Mtb to sustain a chronic infection in C57BL6 mice infected by tail vein injection [5]. These findings are somewhat opposed to the demonstration of activity of TCA1 against biofilm production and chronic TB [3], as well as to the general observation in several microorganisms where biofilm formation is triggered by high c-di-GMP concentration [4]. This is so because deletion of the c-di-GMP PDE is expected to increase second messenger concentrations, which would probably lead to increased biofilm production and, hypothetically, to a sustained, chronic infection. In Vibrio cholerae, to cite one example, compounds that inhibit DGC activity, inhibit biofilm production [6], and it seems worthwhile assessing these compounds during in vivo infection for several model microorganisms. A clear elucidation of a possible relation between inhibitions of biofilm production via new drugs affecting c-di-GMP signaling would help us on the quest for new drug candidates to improve current TB treatment.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11789
  • [From(publication date):
    October-2013 - Nov 21, 2017]
  • Breakdown by view type
  • HTML page views : 7988
  • PDF downloads : 3801
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords