Novel methods improve the detection of antibiotic resistance genes in livestock animals

It is no surprise that antibiotics are widely used in farming for livestock animals or their feed, and their use has led to increased antibiotic resistance. One way to gauge the widespread resistance in animals, and how it spreads to humans is to keep track of the antibiotic resistance genes. The current library to resistance genes consists of known resistance genes and new emerging genes that have not been previously known. The technology and methods used to detect these genes play a vital role in keeping track of this problem.

A study published in journal, Current Opinion in Microbiology focuses on the antibiotic resistant gene detection methods, and how they help us in tracking the spread of this epidemic. Pathogens possessing extended spectrum beta-lactamases (ESBLs), resistance against last line of antibiotics are becoming a huge problem. These ESBLs are mostly isolated in humans; however, they are being discovered increasingly in animal feeds and feces. Their transmission route is still unclear, and this is where these gene detection methods come in to play.

Classic microbiological techniques

      Each cluster represents an individual
      colony of bacteria. Different colors of
      each colony are different species of
bacteria.

Culturing bacteria and PCR-based techniques are becoming a thing in the past with the increasing frequency of newly emerging genes. In bacteria culturing, a sample is grown on a petri dish on an agar layer, and the bacteria present in that sample are analyzed for their identity and genes. While PCR methods are excellent at detecting the known or similar resistance genes, they fail at discovering unknown or distantly related genes. It is scary to think that pathogens may be outrunning our technology. Nevertheless, we are not at a complete loss.

High-throughput technologies

  This figure represents the classic and contemporary
    techniques used for the discovery of antibiotic genes.
   Specialized databases for annotating resistance genes
    are the Antibiotic Resistance gene DataBase (ARDB) and
  the Comprehensive Antibiotic Resistance Database (CARD)

Metagenomic analysis is a novel technology that is increasingly used to analyze the genomic data on antibiotic resistance. This method looks at the entire genetic composition of an environmental sample. Since this technique provides functional gene composition of the pathogens, it can determine novel genomic linkages, phylogenetic information and evolutionary profiles, which makes it easier to spot the mutating genes and arbitrate if that particular gene belongs to a specific pathogen. Because of this method, the way of representing antibiotic genes through Antibiotic Resistance gene DataBase (ARDB) and Comprehensive Antibiotic Resistance Database (CARD) has improved significantly. 

Both techniques have their own advantages and neither should be underestimated. The use of the technique depends on the antibiotic resistance problem and hypothesis of the study.

References:

Allen, H. K. (2014). Antibiotic resistance gene discovery in food-producing animals. Current Opinion in Microbiology, 19, 25–29.

https://www.msu.edu/course/mmg/302/302images/StreakPlt1a.htm

Thomas, T., Gilbert, J., & Meyer, F. (2012). Metagenomics - a guide from sampling to data analysis. Microbial Informatics and Experimentation, 2, 3. 

Is Carbavance our weapon against bioterrorism for antibiotic resistance?

Carbapenem-resistant Enterobacteriaceae are becoming a huge problem in healthcare settings

Bioterrorism has a surprisingly long history dating back to 6th century B.C. to the infamous anthrax scare in 2001. Then again, what exactly is bioterrorism? As the name itself suggests, bioterrorism is an act of purposefully releasing biological organisms to cause disease or death in people. Although no bioterrorist attacks have been reported recently, it is not a completely far-fetched idea. With Ebola epidemic still raging in West Africa due to the lack of proper healthcare facilities, it is not impossible to think that someone can use Ebola virus as a bioweapon to spread this disease in other parts of the world.

As I discussed in my previous blog, antibiotic-resistance organisms are on the rise, and as you can imagine, these organisms can also potentially be used for bioterrorism. Robin Robinson, director of the Biomedical Advanced Research and Development Authority (BARDA) in the U.S. Department of Health and Human Services said that “Antibiotic resistance adversely impacts our nation's ability to respond effectively to a bioterrorism attack and to everyday public health threats.” This year, FDA has been asked twice by U.S. Senators to tighten their trip on the management of antibiotics used for animals in meat industry. Senators believe that monitoring the antibiotic use will allow the government agencies to develop new therapeutics and keep the public health in check.

It is a little relief to see that government is stepping up and taking actions to control antibiotic resistance. Nevertheless, the question arises – how safe are we really? What if there is a bioterrorist attack with multidrug-resistance organisms (MDROs)? How prepared are we to combat this attack? The answer may be right around the corner – Carbavance. Carbavance is a novel antimicrobial drug being developed to treat serious gram-negative bacterial infections. The development of this drug is a joint venture between BARDA and Rempex Pharmaceuticals Inc. Robinson believes that “by partnering with industry to develop novel anti-microbial drugs against biothreats that also treat drug-resistant bacteria, we can address health security and public health needs efficiently.”

Currently, this drug is in its Phase III of clinical trials, and so far, the drug looks promising. One of the most promising factors about Carbavance is that it is a beta-lactamase inhibitor, which works where last defense antibiotics fail. A few of the infections that the drug will be used to treat are urinary tract infection, hospital acquired bacterial pneumonia, ventilator-associated bacterial pneumonia and bacteremia.



References:

The Medicines Company Announces First Patient Enrollment in Phase 3 Studies of CARBAVANCE^TM in Development for the Treatment of Serious Bacterial Infections Due to Gram-Negative Bacteria | Business Wire. (2014, November 5). Retrieved from http://www.businesswire.com/news/home/20141105005423/en/Medicines-Company-Announces-Patient-Enrollment-Phase-3#.VGmNMMnUU0x

Partnership formed to develop Carbavance, a drug against biothreats. (2014, February 5). Retrieved from http://www.upi.com/Health_News/2014/02/05/Partnership-to-develop-drug-against-biothreats-infections/UPI-94611391655526/

Multidrug-Resistant Organisms: A Rising Concern

Welcome to my first blog of Biodefense and infectious diseases! In this blog, I am going to introduce you to a problem that is slowly plaguing our society. If we do not acquaint ourselves with the problem or do not take steps to control the situation, then it may be too late. I am talking about Multidrug-Resistant Organisms (MDROs), also known as “superbugs”. 

What are these superbugs?

Staphylococcus aureus is a very common bacterium that resides on human skin, but it can enter the body through cuts and cause infections. Usually, these infections do not require any special treatments, however, the problem arises when the first-line or commonly prescribed antibiotics are not able to inhibit this organism. MRSA (Methicillin-resistant Staphylococcus aureus) is one of the MDROs that can resist one or more classes of antimicrobial agents. Some of the other common MDROs consist of vancomycin-resistant enterococci (VRE), strains of S. aureus resistant to vancomycin, multidrug-resistant tuberculosis (MDR-TB), multidrug-resistant hepatitis B virus (HBV), and multidrug-resistant HIV. Find out more about these and some other pathogens here.

What makes these pathogens resistant and how can you acquire them?

  Medical illustration of methicillin-resistant
Staphylococcus aureus (MRSA). Centers for Disease
Control and Prevention.

There are multiple ways in which these pathogens acquire resistance against the antimicrobial drugs. Bacteria have a very short life cycle and they multiply rapidly, so if a single bacterium becomes resilient to a drug, it would not take long for the population of that new bacteria to grow and defeat the antibiotic. Another factor that contributes to the emergence of MDROs is the abuse and misapplication of antibiotics. English and Gaur argue that despite a refined healthcare system in United States, misuse of antibiotics occurs due to overly prescribed antibiotics, while in some countries it occurs due to the availability of antibiotics over the counter. In some cases, not adhering to the antibiotic regimen is also responsible for giving rise to resistant pathogens. It is especially true for HIV disease, and missing doses of the HIV medication can cause the virus to mutate and become resistant (“HIV Treatment: Drug Resistance”).

Why should you be concerned?

There are multiple reasons why we should be concerned about these bugs. Shall we look at the casualties? Centers for Disease Control and Prevention has estimated 23,000 deaths and 2 million sicknesses annually due to antibiotic resistant bacteria. If this is not enough, then here are some more reasons:

             Dr. Lance Price, a public health researcher, sheds light on the abuse of antibiotics in farming and how it is affecting us. TEDx Conference, Manhattan, NY.

It is daunting to learn that healthcare facilities are common places to get infected by MRSA and VRE. The microorganisms are transferred through doctors and nurses to patients or through indirect contact with contaminated objects and clothing in the hospital (Bennett). Abrasions or cuts on the skin provide an easy route for these pathogens to enter the body. In the community, athletes and children at daycare are at high risk.

Think about the declining antimicrobial drugs research and how it limits our options of therapeutics against drug resistant infections. Penicillin derived antibiotics have been taken for granted for treating common infections and other diseases, however, due to the evolution of these bugs, there is a dire need for stronger antibiotics as well as awareness among people.

How are you going to stop this epidemic? Stay safe and stay tuned for more information!

References:

• Bennett, G. (2011, August 17). Multi-drug Resistant Organisms (MDROs) in Healthcare Facilities. Presented at the Infection Prevention Conference: Strengthening the fight against HAIs, North Dakota. Retrieved from http://www.ndhealth.gov/disease/hai/Presentation/MDRO.pdf
• English, B., & Gaur, A. (2009). The Use and Abuse of Antibiotics and the Development of Antibiotic Resistance. In Hot Topics in Infection And Immunity in Children VI (Vol. 659, pp. 73–82). Springer. Retrieved from http://download.springer.com.mutex.gmu.edu/static/pdf/42/bok%253A978-1-4419-0981-7.pdf?auth66=1411007368_9bedb762ed6caf44893443ffff3fd2a7&ext=.pdf
• HIV Treatment: Drug Resistance. (2014, May 6). Retrieved from http://aidsinfo.nih.gov/education-materials/fact-sheets/21/56/drug-resistance
• CDC - National Strategy - Antimicrobial Resistance. Retrieved from http://www.cdc.gov/drugresistance/national-strategy/index.html
• Newsroom Image Library - Disease Agents | CDC Online Newsroom | CDC. Retrieved from http://www.cdc.gov/media/subtopic/library/diseases.htm