Difference between revisions of "Part:BBa K1927000"

Revision as of 08:12, 14 October 2016

Usage and Biology

This biobrick contains an ESBL gene called blaNDM-1 E.Coli which represent class B carbapenemase of the ESBL group. It belongs to a rather big group of extended spectrum β - lactamases (ESBL). Bacteria that produces these enzymes are resistant to several types of antibiotics. Classification of ESBL is done in many ways and is rather complicated. Different nomenclatures have been proposed and depated for beta lactamases which includes several hundreds of enzymes.(http://www.lahey.org/studies/webt.asp) Carbapenemase is a versatile group of beta lactamases, they have the abitily to hydrolyze penicillins, cephalosporins, monobactams and cabapenems. For this reason these bacteria can cause serious infections in humans. Carbapenemases are further divided into molecular classes A, B and C. This particular gene belongs to class B which represent metallo-beta-lactamases that contain zink in the active site. The gene has been shown to spread at an unprecedented rate because it has been identified not only in single species but also in unrelated species.

UiOslo’s project will focus on a particular antibiotic resistance mechanism caused by extended - spectrum beta lactamase (ESBL). This is also the reason for generation of this biobrick. These type of enzymes was first detected in 1979 and the prevalence of these ESBL producing bacteria have gradually increased in hospitals and other health care institutions.

The majority of E. Coli ESBL infections are represented by urinary tract infections, but they can also cause other severe infections in the blood stream and the central nervous system. The mechanism for antibiotic resistance is usually the same among different EBSL producing bacteria. It is based on the same principles as other beta lactamases. They have the ability to hydrolyze the beta lactam ring that is the “active site” to several types of antibiotics such as Penicillin derivatives, third - generation cephalosporins and axtreonam. In addition to this, ESBL producing bacteria exhibit co-resistance to many other classes of antibiotics which makes these kinds of infections challenging to treat. Thus, there is need for efficient detection methods and development of better antimicrobal agents among towards these organisms.

Beta lactam antibiotics exhibit the most common treatment for bacterial infections both in Norway and worldwide. Thus, the resistance to beta - lactam antibiotics among gram - negative bacteria is a worldwide problem. At the level of a wider geographic scale, the incidence of ESBL-producing organisms is difficult to resolve due to various reasons, difficulty in detecting ESBL production and inconsistencies in reporting (Steward et al., 2000). Recently, a significant increase in the incidents of ESBL-related infections has been observed throughout the globe (Rupinder et al., 2013, Abhijit et al., 2013, Majda et al., 2013, Meeta et al., 2013, Kritu et al., 2013,Fatemeh et al., 2012 and Gupta, 2007).

In Norway an antibiotic resistance centre in Tromsø generate a comprehensive report each year on the status of antibiotic resistance from all over Norway. First figure displays the prevalence of resistance towards different antimicrobal agents in urinary tract infections in Norway from 2002 to 2014. ESBL numbers here are quite low for now compared to ampicillin, but increases every year.

This figure displays the precalence of ESBL among E. Coli and K. spp isolates recorded from 2003 - 2014. The green line represents ESBL prevalence in urinari tract infections. From 2013 to 2014 the prevalence has doubled and the increase is exponential. This is why a fast and easy detection method is needed on the market today, so that it may be easier to detect these cases and by detecting them early it will reduce the discomfort of the pasient as well as have a bigger chance of getting rid of the infection before it continues to spread.