Antibiotic Resistance: Super-Bugs Causing Super-Problems
By Amanda Riley
Imagine you’re an extremely sick patient in a hospital. Doctors have been prescribing medicines to try to treat you, but nothing is working. This is a scary situation—for doctors and patients alike—and it is occurring all over the world because of antibiotic resistance, but not enough is being done to address this problem. That stops now; it’s time to increase awareness about the severity of antibiotic resistance!
Antibiotics are meant to stop the growth of harmful bacteria in a host (such as a human) [1]. One class of antibiotics called beta-lactams (so-named because on the shape of the molecule) accomplish this by interfering with a bacterial cell’s ability to synthesize cell walls [2]. In a bacterium, the cell wall is equivalent to the foundation of a house. Without sturdy building materials, you can’t build a house, and without proper cell wall proteins, bacteria will fall apart [2]. In a properly functioning bacterium, Penicillin Binding Proteins (PBPs) are instrumental for building cell walls [2].
Interaction of beta-lactam antibiotic with PBP - Photo credit: http://hiv.uw.edu/images/derm/DM6_d03c.png.
Beta-lactam antibiotics interfere with this process by binding to PBP; essentially, the antibiotic is getting in the way of PBP such that PBP can’t perform its job (see Image 1) [2]. Once the antibiotic is bound, the bacterial cell wall crumbles and the cell dies [2]. One of the most well known examples of this class of antibiotics is penicillin (how the membrane receptor got its name!), and there is no doubt that penicillin and other antibiotics are useful medicines [2]. However, some bacteria (deemed “super-bugs”) have developed clever ways of becoming resistant to antibiotics.
In terms of the beta-lactam mechanism described above, some bacteria are able to produce proteins called beta-lactamases, which break down the beta-lactam antibiotic [2]. This frees up PBP, prevents the cell wall from breaking down and keeps the bacterium alive [3]. One resistant cell doesn’t pose many problems, but bacteria can “share” resistance [4]. In all cells, instructions for making proteins—such as beta-lactamases—are encoded as genes in the DNA [5]. Bacteria can store antibiotic resistance genes on pieces of DNA called plasmids, which can be shared with other bacteria (see Image 2) [5]. This allows antibiotic resistance to spread quickly among populations of bacteria, and scientists are racing to find ways to slow down this process.
Thousands of bacterial species exist [6] and more are being discovered, but a recent study focused on one strain in particular: Acinetobacter baumannii, commonly found in hospital Intensive Care Units and linked to serious infections such as pneumonia [7]. Researchers found that 91.1% of tested strains were resistant to several antibiotics [7].
Transfer of antibiotic resistance. The yellow region represents the antibiotic resistance gene.
Photo credit: http://www.usatoday.com/story/news/nation/2012/11/29/bacteria-deadly-hospital-infection/1727667/
Mechanisms of resistance in this strain of bacteria are complex, but attention is being drawn to a class of beta-lactamases called carbapenemase enzymes [7]. Researchers have identified a specific plasmid in A. baumannii that stores carbapenemase genes and allows antibiotic resistance to spread efficiently in populations of this bacteria, thus making A. baumannii infections very difficult to treat [4]. This study was conducted in China, but bacteria don’t need passports; they can easily travel all over the world!
According to reports by the Centers for Disease Control and Prevention, antibiotic resistance causes 2,049,442 illnesses and 23,000 deaths in the United States annually [8]. What’s being done about this? New medicines could be part of the solution, but as of this past March, only 36 antibiotics were being developed [9]. This might seem promising, but it can take over 10 years for a drug to even make it to the clinical trial stage and then typically only 1 out of every 5 drugs that reach this point will attain FDA approval [10]. Antibiotic resistance research can be intimidating due to its complexity and cost, but research breakthroughs can lead to thousands of lives being saved.
If we can increase public awareness about this problem, then together we can develop ways to promote anti-bacterial therapy. Vaccines are promising because if a vaccine can protect someone from being infected with a bacterial disease, then we can begin to reduce our dependence on antibiotics [11]. After you finish reading this article, get the word out and talk to your friends and family about antibiotic resistance! We also need to advocate for collaboration and data sharing among universities, hospitals, and pharmaceutical companies because antibiotic resistance is a global problem. Pooling resources and minds will accelerate the research process! One person infected with a “super-bug” can spread that infection to countless others, and we need to have the proper tools to prevent a pandemic before it starts.
References
1. Lin J, Nishino K, Roberts MC, Tolmasky M, Aminov RI, Zhang L. Mechanisms of antibiotic resistance. Front Microbiol. 2015;6:34. doi: 10.3389/fmicb.2015.00034. PubMed PMID: 25699027; PubMed Central PMCID: PMCPMC4318422.
2. Cho H, Uehara T, Bernhardt TG. Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell. 2014;159(6):1300-11. doi: 10.1016/j.cell.2014.11.017. PubMed PMID: 25480295; PubMed Central PMCID: PMCPMC4258230.
3. Shaikh S, Fatima J, Shakil S, Rizvi SM, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi J Biol Sci. 2015;22(1):90-101. doi: 10.1016/j.sjbs.2014.08.002. PubMed PMID: 25561890; PubMed Central PMCID: PMCPMC4281622.
4. Liu LL, Ji SJ, Ruan Z, Fu Y, Fu YQ, Wang YF, et al. Dissemination of blaOXA-23 in Acinetobacter spp. in China: main roles of conjugative plasmid pAZJ221 and transposon Tn2009. Antimicrob Agents Chemother. 2015;59(4):1998-2005. doi: 10.1128/AAC.04574-14. PubMed PMID: 25605357; PubMed Central PMCID: PMCPMC4356780.
5. Using medication: Using antibiotics correctly and avoiding resistance U.S. National Library of Medicine 2013 [updated 18 December 2013]. Available from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072621/.
6. Mora C, Tittensor DP, Adl S, Simpson AG, Worm B. How many species are there on Earth and in the ocean? PLoS Biol. 2011;9(8):e1001127. doi: 10.1371/journal.pbio.1001127. PubMed PMID: 21886479; PubMed Central PMCID: PMCPMC3160336.
7. Jia W, Li C, Zhang H, Li G, Liu X, Wei J. Prevalence of Genes of OXA-23 Carbapenemase and AdeABC Efflux Pump Associated with Multidrug Resistance of Acinetobacter baumannii Isolates in the ICU of a Comprehensive Hospital of Northwestern China. Int J Environ Res Public Health. 2015;12(8):10079-92. doi: 10.3390/ijerph120810079. PubMed PMID: 26308027; PubMed Central PMCID: PMCPMC4555330.
8. Antibiotic/Antimicrobial Resistance Centers for Disease Control and Prevention 2015 [updated 08 September 201513 September 2015]. Available from: http://www.cdc.gov/drugresistance/about.html.
9. Tracking the Pipeline of Antibiotics in Development The Pew Charitable Trusts 2015 [updated 28 July 201513 September 2015]. Available from: http://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2014/03/12/tracking-the-pipeline-of-antibiotics-in-development.
10. Hay M, Thomas D, Craighead J, Economides C, Rosenthal J. Clinical development success rates for investigational drugs Nature Biotechnology 2014;32(1):40-51.
11. Gelband H, Laxminarayan R. Tackling antimicrobial resistance at global and local scales. Trends Microbiol. 2015;23(9):524-6. doi: 10.1016/j.tim.2015.06.005. PubMed PMID: 26338444.
Amanda Riley - Muhlenberg Class of 2016
Amanda Riley ('16) is a senior Biology major at Muhlenberg College with minors in French and Public Health.
After college, she's interested in pursuing a career as a research scientist but is hoping to gain more work experience before going to graduate school. She's had internships within the pharmaceutical industry and also within academia, but she would like to continue learning about fields of biomedical research.
Working with influenza vaccine during a previous internship was a challenging but rewarding experience that made her think about pursuing vaccine development.
Wherever her career takes her, she hopes to have the opportunity to travel. She studied abroad in Geneva, Switzerland during the Spring 2015 semester and had an incredible time! She took public health and french classes, lived with a french-speaking homestay family, visited international organizations (including the World Health Organization!) and traveled with friends.
She would love to return to Europe someday, maybe working as a research scientist!