MECHANISM OF DRUG RESISTANCE IN NEISSERIA GONNORRHOEA
Neisseria gonorrhea, originally high susceptible to antibiotic can adapt to adverse condition. (Johnson and Morse 1988). A hostile environment in which antibiotic are present may select; for the multiple change which result in resistance and treatment failure.
Mechanism of antibiotic resistance in gonococcus may be conveniently group as those that involve alteration of the target site. Access of antibiotic to the target site may be limited by reduce permeability of the cell envelope caused by change in porin proteins; active export of antibiotic from the cell by means of efflux pumps; and destruction of the antibiotic before it can interact with the target site. (Sparling 2005).
Alteration or deletion of the target site of the antibiotic result in a reduction of its affinity for the antibiotic. Generally, these changes may be mediated by either chromosomal or extra-chromosomal elements (plasmids). Multiple resistance determination may co-exist in a single organism so that level of resistance can increase incrementally and a single strain can be resistant to a number of different antibiotics.
In Neisseria gonorrhea, the process of genetic transformation is known to be responsible for acquiring drug resistance. But such a change is visible only if many such acquisitions of the determinant take place. (Johnson and Morse, 1998). Plasma mediation resistance, at present limited to penicillin and tetracycline, is transmitted by means of conjugation. This process requires the presence of a conjugative plasmid to mobilize the plasmid carrying the resistance determinants.
Since not all strain posses conjugative plasmids, the rate of spread of resistance may be limited to some extent. However, conjugative plasmids are also transferable during conjugation, so that some recipient strain then becomes donor themselves. Among non-quinolone drugs, several studies have been carried out to understand the mechanism of penicillin resistance in N. gonorrhea, this is summarized below.
RESISTANCE OF NEISSERIA GONORRHOEA TO PENICILLIN
Penicillin was widely used from the treatment of gonorrhea for many years (and is still in use in some regions). Originally, Neisseria gonorrhea was extremely sensitive to almost all the drugs known so far, and treatment with 150,000 units of penicillin was effective in most instances. Later on decreased in Vitro susceptibility towards penicillin appeared and it was thought to be associated with treatment failure (Reyn et al, 1958). Increasing the recommendation dose of penicillin temporarily alleviated the clinical problem resulting from infection with these strain, but almost inexorably levels of resistance increased and large number of treatment failure occurred again even with high-dose regimens(Sparling 2005).
A vivid example is the targets of B-lactum agents are the Penicillin Binding Protein (PBPs), enzyme located in the cell envelops that participate in cell wall metabolism. Alteration in PBPs-2 and PBP-1 decrease their affinity for the penicillin’s and thus, the susceptibility of the organism. PBP-2 is encoded by the PenA locus (Sparling et al, 1999). Change in other locci such as mtr and PenB produce additive effect. The mtr locus mediates resistance to a wide rage of antibiotics, detergents and dye through an active efflux system.
Neisseria gonorrhea is also resistance to some other drugs apart from penicillin; some of which include tetracycline, quinolone and cephalosporin, in which the access of quinolones to their target is reduced by changes in cell permeability and possibly by efflux mechanisms. The target of quinolone are topoisomerase in the organism (Neisseria gonorrhea), these include DNA gyrase. (Weidman and Heisig, 2008).
