Seminario Biología

Leonardo EchavarríaYeison Cantor

INTRODUCTION

• the kind of bacteria that can be cultivable in the laboratory represent 1% of the different species found in the environment, Because of this the researchers developed in situ cultivation techniques or using specific growth factor allowing better result with uncultured bacteria.

ANTIBIOTIC RESISTANCE

Resistance occurs by natural selection through random mutations

• Drug inactivation or modification• Alteration of target site• Alteration of metabolic pathway• Decreasing drug permeability or increasing

active efflux

TEIXOBACTIN• Teixobactin is a depsipeptide which contains

enduracididine, methylphenylalanine, and four D-amino acids produced by Eleftheria terrae

MECHANISM AND RESISTANCE

BACTERIA

• The most representative characteristics of gram – and gram + bacteria are the thick o the cellular wall, flagellum , interaction with antibiotics and the stain with Christian Gram coloration.

+ Staphylococcus aureus: folliculitis, furunculosis, deep abscesses, osteomyelitis, meningitis, sepsis, endocarditis and pneumonia.

• Streptococcus pyogenes: Tonsillitis and impetigo.

• Clostridium botulinum: botulism.

• Enterococcus faecalis: Endocarditis, bladder infections, prostate and epididymis.

• Bacillus anthracis : carbunco.

⁻ Escherichia coli : Excretory system infections, urinary tract infections, cystitis, meningitis, peritonitis, mastitis, septicemia and pneumonia.

• Salmonella enteritidis: Acute gastroenteritis.

• Helicobacter pylori: Gastritis (stomach ulcers) and gastric cancer.

• Haemophilus influenzae: Meningitis, epiglottitis, pneumonia and sepsis.

• Legionella pneumophila: legionellosis. (pneumonia and high fever).

OBJECTIVES

• Determine the optimal conditions for growing the Eleftheria Terrae

• Identify the genetic sequence of teixobactin

• Describe the metabolic route of synthesis of Teixobactin

• Describe the mechanism of antimicrobial action on microorganisms with proven resistance to antibiotics

• Test antimicrobial efficacyTeixobactin.

METHODS

• ISOLATION AND CULTIVATION OF PRODUCING STRAINS: the purpose is to prepare an appropriate culture medium to purify later

MUSE LUNG INFECTION MODEL

EXTRACT PREPARATION AND SCREENING FOR ACTIVITY

• visible clearing zones indicated antibacterial activ.ity

MINIMUM BACTERICIDAL CONCENTRATION

MINIMUM INHIBITORY CONCENTRATION

• the lowest concentration of antibiotic with no visible growth.

BIOSYNTHETIC GENE CLUSTER IDENTIFICATION.

STRAIN FERMENTATION AND PURIFICATION OF TEIXOBACTIN.

• Extract lyophilized sustrate.

SEQUENCING OF THE STRAIN

TIME-DEPENDENT KILLING

• preparations to compare with other antibiotics

RESISTANCE STUDIES

• measure activity against old resistant bacteria and possibly new development.

RESULTS

Gavrish, E. et al. Lassomycin, a ribosomally synthesized cyclicpeptide, killsMycobacterium tuberculosis by targeting the ATP-dependentproteaseClpC1P1P2. Chem. Biol. 21, 509–518 (2014).Wilson, M. C. et al. Anenvironmentalbacterialtaxonwith a large and distinctmetabolicrepertoire. Nature 506, 58–62 (2014).Doroghazi, J. R. et al.Aroadmapfor natural product discovery based on large-scalegenomics and metabolomics. NatureChem. Biol. 10, 963–968 (2014).

IN AGREEMENT WITH THE STUDY

The authors concluded that the MO grown using this technique suitable for the development of new antibiotics

Forsberg, K. J. et al. Bacterial phylogeny structures soil resistomes across habitats.Nature 509, 612–616 (2014) IN AGREEMENT WITH

THE STUDY

Transmission of resistance by horizontal phylogeny

Conlon, B. P. et al. ActivatedClpPkillspersisters and eradicates a chronicbiofilminfection. Nature 503, 365–370 (2013)

IN AGREEMENT WITH THE STUDY

Mechanism of drug action by a non-specified protease which hydrolyses the cell wall.

Schneider, T. &Sahl, H. G. Anoldiebut a goodie—cellwallbiosynthesis asantibiotic target pathway. Int. J. Med. Microbiol. 300, 161–169 (2010)

IN AGREEMENT WITH THE STUDY

Exploit the weaknesses of bacteria to develop better antibiotics less prone to development of resistance.

CONCLUSIONS

• ICHIP TECHNOLOGY WILL ALLOW NEW PROBE ON MICROORGANISMS AND NEW ANTIBIOTICS

• TEIXOBACTIN PROMISES TO BE AN ANTIBIOTIC THAT SAVED THOUSANDS OF LIVES

• IN THE OUTSIDE WORLD THERE ARE A LOT OF MICROORGANISMS THAT ARE WAITING TO BE DISCOVERED AND STUDIED REVEALING LOTS OF UTILITIES AND RELATED TO MEDICINE HELPING TO INCREASE THE EFFECTIVENESS OF DRUGS TREATMENT.

• JOINING FORCES BETWEEN DOCTORS, POLITICIANS AND THE COMMUNITY IN GENERAL TRYING TO MAKE POSSIBLE DECREASES OF BACTERIAL RESISTANCE AND PREVENT DANGEROUS PATHOGENS THAT THREATENS EVERYONE

GRACIAS