Antibiotic Resistance: Combating An Important Problem

A high concentration of cationic peptides destroying the integrity of a bacterial membrane

A high concentration of cationic peptides destroying the integrity of a bacterial membrane

The antibiotic is a cornerstone of today’s medical treatment, but with the increasing rate of bacteria that are steadily growing impervious to these chemical treatments, should we consider the other options as valid alternatives? [1]. Starting in the 1920’s with the discovery of penicillin, a surge of antibiotic discovery enveloped the scientific world as scientists efficiently developed new and effective treatments [2]. With such widespread use of antibiotics, bacteria inevitably developed resistance to new chemicals. Up until the 1980’s, scientists were able to combat these adaptations, but innovation slowed immensely due to scientific, economic, and political limitations [2]. Antibiotic-resistance has grown exponentially ever since [2]. Utilization of cationic peptides, bacteriophages, and probiotics are three effective and innovative forms of therapy that society must capitalize on in light of antibiotics’ inevitable decline [1].

The use of cationic peptides is one very effective option in dealing with bacterial infection. These short peptides consisting of fifteen to fifty amino acids function by distorting the membranes and even directly attacking major components within the cytoplasm [4]. A cationic peptide first compromises the outer membrane in bacteria by displacing magnesium ions; this process makes the cell negatively-charged [5]. The cationic peptide attracts the now negatively-charged membrane, and in the process distorts the membrane and permeates across [5]. Next, the polymer becomes parallel to the membrane and folds into the membrane-bound structures [5]. This positioning allows the peptide to create channels that push impurities into the bacterium, break down the membrane’s integrity completely, or even attack specific compounds within the cell [4].

A major benefit of peptide technology is the specificity with which these chemicals operate when combined with one another. The success of peptide specificity is evident in experiments with rabbits’ joints, wherein specific bacteria that cause various forms of synovitis (inflammation of joint lining) were eradicated when the two peptides HAP-1 and (KLAK)2 were introduced [6]. Also cationic peptides derived from existing tumor suppressor genes like p16 have been shown to limit tumor growth in lab-rat models when they are merged with atennapedia peptides, proteins that control the formation of bodily structures [6].

The cost of peptide technology is currently what prevents this innovation from cementing itself as a reliable alternative [4]. Cationic peptides do cost a considerable amount of money to synthesize and utilize, but over time, with new research and innovations in the field, the price of this alternative will surely decrease much in the same way antibiotics did after their inception [1].

Another potential alternative to antibiotic treatment is the employment of probiotics. Essentially, probiotics are friendly bacteria that benefit the host [3]. Just a few of the many benefits that probiotics provide are promoting the absorption and production of vitamins and enabling efficient inflammatory responses [8]. Lactobacillus acidophilus is a common probiotic already present the bodies of yogurt consumers; the power and duration of the benefits of consuming yogurt are well documented and demonstrate that probiotics are an efficient and non-toxic method for promoting good health and preventing disease [8].

Studies have revealed that intentionally injecting probiotics into a biological system produces results that are exponentially larger and rival the protection offered by antibiotics [7]. In an aquaculture study in Nigeria, when various strains of probiotics were injected into organisms, the microbes produced inhibitors that destroyed pathogens and crowded out invading bacteria as well [8]. Probiotics take resources from pathogens and provide protection, all the while promoting growth throughout the entire body, especially the intestinal tract. Probiotics effectively address the concern of antibiotic resistance as pathogen adaptation is ineffective; various trials indicate that overtime, the invading bacteria in the organism was unable to change and respond to the living probiotics [1]. They are also cost-effective due to their availability in the environment [1]. Unlike antibiotics, which sometimes require toxins to eradicate bacteria, probiotics provide sustained treatment over a long period of time and without the use of any toxic elements [7]. In the near future, probiotics can be seen as a viable source for treatment against malignant bacteria so long as research in the field develops to encompass more beneficial strains.

While probiotics take a more indirect approach to eradicating disease, bacteriophage therapy poses a more straightforward solution that also has the potential to become more widespread in due time [9]. Bacteriophage therapy uses specific viruses that infect bacteria directly. These phage particles are narrow spectrum agents —that is, they possess the mechanism to infect specific strains of bacteria through their inherent properties, as well as to manipulate DNA [3]. Phages enter a cell, reproduce within the bacterium, and eventually accumulate and burst the cell open [9].

The study of phage therapy began around the same time as antibiotics in the 1930’s and 40’s. Early experiments suggested that antibiotics were more reliable and consistent when compared to phage therapy’s results [10]. As time progressed, bacteriophage therapy became a prime example of how time allocated to research can yield amazing new findings and innovation [10]. Present findings demonstrate many benefits of bacteriophage therapy that antibiotics simply do not possess. Bacteriophage therapy is very cost effective as phages are everywhere in the environment and simple to obtain. The viruses only destroy specific targets — much like peptides — yet do not harm the beneficiary bacteria or microorganisms [9]. Also, phage therapy is long-lasting, as the virus is able to remain inside the organism and destroy invaiding bacteria over an extended period of time [1]. Bacteriophage therapy can pose some problems if viruses are not purified properly, but if research is increased and thoroughness is maintained, this treatment will become a new standard as antibiotics’ prevalence deteriorates [10].

The societal implications of these new forms of therapy are essential to understanding the need to resort to innovative alternatives. “At a time when the frequency of infections caused by antibiotic- resistant bacteria is rising sharply, the pool of antibiotics in development by drug companies is drying up,” states Michael A. Schmidt, a professor at Columbia University Medical Center [11]. The FDA has only approved an average of 3 antibiotics per year from 1988 to 1992 and this number has fallen to one approval per year since 2003. The lack of new antibiotics during the time that they are needed the most is due to the shift in focus of these pharmaceutical companies. They are focusing on large markets in the drug industry that correlate with chronic conditions (diabetes, depression, arthritis) that will make them a large sum of money from the necessary long-term therapy [11].  Alternatives for antibiotics should be the focus of the drug companies as the threat of antibiotic-resistance is growing exponentially each day.

The uses of peptides, probiotics, and bacteriophages are three very realistic methods that have the potential to be leaders in the race for new disease treatments, if enough time is allocated for their development. Their efficiency and realistic cost are reasons why these alternatives should be the focus of modern medicine’s focus. The same invigoration and passion for discovery that was present during the foundation of antibiotic research is very much needed today if society is ever going to battle the problem of finding new forms of therapy to replace the ill-fated antibiotics [2]. A new era of treatments is on the horizon and must be ushered from experimental procedures to societal standards to preserve the future of the globe’s healthcare system [3].

References

  1. Joerger RD. Alternatives to antibiotics: bacteriocins, antimicrobial peptides and bacteriophages. Poultry Science. 2002 Nov 11;82:640-647
  2. Interlandi J. Are we running out of antibiotics?. Newsweek. 2010 Dec 13; 156(24):42
  3. Kardar SS. Antibiotic Resistance: New Approaches to a Historical Problem [Internet]. Emory University, American Institute of Biological Sciences; 2005 March [updated 2008 Feb]. Available from: http://www.actionbioscience.org/newfrontiers/kardar.html
  4. Wilcox S. The new antimicrobials: Cationic peptides. BTJ. 2004 Fall; 2(1):88-91
  5. Bell TW. Carriers  and  channels: Current  progress  and  future  prospects. CO Chemical  Biology. 1998; 2:711-716
  6. Langel U. Handbook of cell-penetrating peptides. Oxford: CRC Press; c2007. 600 p.
  7. Chukeatirot E. Potential use of probiotics. Songklanakarin J. Sci. Technol. 2003 Mar-Apr;25(2):276-282.
  8. Kondadacha OD, Adikwu IA, Okaeme AN, Atiribom RY, Mohammed A,  Musa YM. The role of probiotics in aquaculture in nigeria: A review. Wilolud Journals. 2011 Jan;5(1):8-15.
  9. Marsa L. Enlisting viruses to battle bacteria. Los Angeles Times. 2003 Mar 31:F3.
  10. Ho K. Bacteriophage therapy for bacterial infections: Rekindling a memory from the pre-antibiotics era. Perspectives in Biology and Medicine. 2001 Jan 16;44(1):253-255, 513.
  11. Schmidt MA Beyond Antibiotics: Strategies for Living in a World of Emerging Infections and Antibiotic-Resistant Bacteria. Berkeley: North Atlantic Books; 2009.
  12. Sullivan JM. R.E.W. Hancock Laboratory – Peptides. [homepage on the Internet]. 2000 [cited 2012 Jan 19]. Available from: University of British Coloumbia, R.E.W. Hancock Laboratory Web site: http://www.cmdr.ubc.ca/peptide2.jpg

Sartajdeep Kahlon is a student at The Harker School in California, a part of The Triple Helix high school chapter program. Follow The Triple Helix Online on Twitter and join us on Facebook

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  • Bill Riedel

    Considering the large amount of scientific information that is available on phage therapy, it is my opinion that phage therapy should be offered to patients suffering from bacterial infections when antibiotics fail. In my opinion the most important discussion we need to have is: What are the moral, ethical, legal and economic issues when phage therapy is not made available to patients when antibiotics fail? ( It is my opinion that every infection control specialist can reasonably be expected to be knowlegible of the scientific validity of phage therapy).

  • B19003

    too long, did not read