So if you have read my previous post on how a new antibiotic was discovered, then hopefully you have an insight into the issue of antibiotic resistance - but actually, what is antibiotic resistance?
The antibiotic age began in the 1940s, when penicillin became available for use to treat infections. Now, this is surely a key moment in medicine! - however, the bacteria soon found ways to become resistant to these antibiotics, i.e. the bacteria find ways to make the antibiotic ineffective. As time has gone on, new antibiotics and antibiotic classes were being found, however this is not the case today. Therefore, we are in a situation where antibiotics are gradually becoming ineffective, but at the same time there are no new classes of antibiotics being introduced into clinical use. This is worrying for sure!
Antibiotics are generally divided into "classes" based on their structure, as well as how they target the bacteria. For example, penicillin belongs to the beta-lactam class of antibiotics, which are a group of antibiotics which target the cell wall of the bacteria. Erythromycin is a macrolide, which is a group of antibiotics which stops bacteria making proteins. Another aspect of bacteria which can be targeted is the synthesis of DNA, which fluoroquinolones like ciprofloxacin do.
While some bacteria can naturally be resistant to antibiotics, others are not. The worry is that the bacteria which are susceptible to antibiotics are gaining resistance to antibiotics, sometimes to multiple antibiotics. This can happen in several ways; by pumping out antibiotics, by gaining new genes which enable the bacteria to break the antibiotic, or by changing the antibiotic target/gaining an alternative to the target. There can be multiple resistance mechanisms for a single antibiotic too!
In the bacterium Staphylococcus aureus, it was found that one way of becoming resistant to fluoroquinolones was to make more pumps, which meant that the antibiotic was being moved out of the cell before it had time to affect the cell.
S. aureus was initially susceptible to penicillin, however the use of penicillin in the clinic lead to the bacterium acquiring a gene which enabled it to break penicillin (beta-lactamase/penicillinase). This lead to the creation of methicillin, which is insensitive to beta-lactamase. S. aureus fought back against this new antibiotic by acquiring the mecA gene, which is an alternative to the beta-lactam target (PBP). Therefore, S. aureus with mecA can survive in the presence of methicillin because mecA gene makes a PBP, BP2', which is not blocked by methicillin or other beta-lactams and thus can take over from the other PBPs which have been blocked. This is what makes S. aureus MRSA (Methicillin-Resistant S. aureus).
Mupirocin is another antibiotic which S. aureus can be resistant to, but this occurs as "low-level" and "high-level". In low-level mupirocin resistance, the target (IleS) is changed so that it still works without allowing mupirocin to bind. However, high-level resistance is mediated by the acquisition of the mupA/ileS-2 gene, which does the same thing as IleS but is not affected by mupirocin at all. So, this shows that there are multiple ways of becoming resistant to one antibiotic!
OK, this is a lot longer than I had anticipated, but hope you found it informative!
Thanks for reading,
Maho
Sources:
"Mechanisms of Antimicrobial Resistance in Bacteria", F. Tenover - The American Journal of Medicine 2006, 119:6, S3-S10
"Waves of Resistance: Staphylococcus aureus in the Antibiotic Era", Henry F. Chambers and Frank R. DeLeo - Nature Reviews Microiology 2009, 7, 629-641.
"Clinical Relevance of Mupirocin Resistance in Staphylococcus aureus", D. J. Hetem and M. J. M. Bonten - Journal of Hospital Infection 2013, 85:4, 249-256