Q8 How does horizontal gene transfer contribute to problems of health-care associated infections?

Q8 How does horizontal gene transfer contribute to problems of health-care associated infections?

Answered by Michelle Hoile

General Information

* Horizontal gene transfer is the movement of genetic information from one organism to another without being the offspring of that organism. The most common examples are seen between bacteria.
* Methicillin-resistant Staphylococci, vancomycin resistant Enterococci (VRE) and extended-spectrum beta-lactamase (ESBL) producing Gram negative bacilli are major nosocomial pathogens
* Three mechanisms of horizontal gene transfer exist- transduction, transformation and conjugation
* In health care environments, the problem associated with horizontal gene transfer is antibiotic resistance
* There are a number of changes that can occur in bacteria to cause them to become resistant; altered binding site, inhibition of metabolic pathways, increase in the rate of efflux of antibiotic out of bacteria, change in membrane permeability so antimicrobials can’t bind and production of enzymes that destroy or inactivate the drug
* There are a number of factors which contribute to the spread of health care associated antibiotic resistance: a combination of microbial characteristics, the selective pressure of antimicrobial use, and social and technical changes that enhance the transmission of resistant organisms.



Microbial characteristics

* There is strong evidence that the horizontal transfer of resistance genes contribute largely to the emergence of multidrug-resistant Enterobacteriaceae (most common =VRE)
* Enterococcal resistance includes beta-lactamase-mediated resistance, ampicillin

resistance based on altered penicillin-binding proteins (PBP), and high-level aminoglycoside resistance

* ESBL producing Gram-negative bacilli are of special clinical concern, as they may transfer resistance gene to other, more pathogenic bacterial genera
* MRSA has been a continual and there is an emerging threat of vancomycin resistant and intermediate resistant MRSA. MRSA is found in 60% of ICU patients
* Mutation in genes encoding for MMR proteins in bacteria are associated with increased resistance in health care enviroments
* MMR proteins normally recognize mismatched bases in the DNA and abort recombination process between diverged DNAs. Thus MMR is a potent inhibitor between non-identical sequences. MMR system is also involved in the control of DNA

replication fidelity. Therefore inactivation of MMR gene should increase the probability of any gene transfer between diverged bacteria (eg, antibiotic resistance gene).

* Numerous mutator E. coli, Salmonella enterica and P aeruginosa isolates from

patients have defective MMR systems

* Studies have demonstrated that the transfer of antibiotic resistance genes can take

place in the intestine between a variety of different gram positive or Gram-negative bacilli… and if an antibiotic resistant strain arises I assume it will flourish is immunocomprimised patients

Selective Pressure

* Overuse of antibiotics, especially in intensive care units- there is a higher incidence of antibiotic resistance in ICUs
* Inadequate use of antibiotics contributes to increased bacterial resistance both by selecting

for the more resistant members of a population and by eliminating the patient’s resident flora

* Immunocomprimised patients



Social and Technical Changes

* Lapses in infection control practices leading to increased transmission of resistant organisms-thus the application of strict prevention strategies, including changes in antibiotic treatment regimens, hygiene measures and infection prevention is essential to reduce antibiotic resistance
* Increase use of invasive devices and procedures
* Greater number of susceptible hosts- because we have an array of devices to keep very ill people alive

Conclusion

o Horizontal gene transfer provides a means for bacteria to develop antibiotic resistant properties. Selective pressure in the health care setting has increased the incidence of an array of antibiotic resistant bacteria.
o This has been demonstrated by major drug resistant nosocomial pathogens (MRSA, VRE and EBSL), where studies have shown that their drug resistant properties have most likely arisen from horizontal gene transfer



Note: Random gene mutations may also produce drug resistant strains of bacteria but this is not horizontal gene transfer

Horizontally transferred genes are often flanked by IS sequences which often contain virulence genes such as antibiotic resistance…thus in my opinion, horizontal gene transfer is more common than point mutations in contributing to drug resistance.