The Spread of a Drug-Resistance Gene

Question 1 

Antibiotic therapy reveals the existence of drug-resistant bacteria in various ways. First, there will be no response to the antibiotic used in a previously sensitive condition meaning the bacteria has developed resistance and thus insensitive to the same drug regimen; hence it is still growing. In such cases, the patient condition worsens. This would then mean other drug classes are attempted to treat the condition caused by a resistant bacterium which may again prove not responsive to the agents, thus suggesting the existence of a drug-resistant bacteria (Reygaert, 2018). Second is when higher dosages are required to attain therapeutic goals than previous dosages. In other cases, the need for extended duration of antibiotic therapy than was used previously points to the presence of a drug-resistant bacteria. 

Question 2 

This might have happened through transposition where the resistant material had moved from the chromosome to the plasmid with the transposon containing multiple antibiotic resistance genes as the woman was hospitalized in an area with a high prevalence of the resistant New Delhi Metallo-beta-lactamase ( NDM ) gene (Heinze, 2019). With the resistant genes encoded on the plasmid with multiple resistance gene clusters and also easily transferred to bacteria in other genus. This most likely took place via conjugation where through the sex pilus, the plasmid DNA was exchanged through horizontal gene transfer as is the case with most gram-negative bacteria in which Klebsiella bacteria belong (Navon-Venezia et al., 2017). 

Question 3 

Abundant amounts of inserted genetic sequences point to the fact that the plasmid may have acquired the resistant genes through gene transposition process. This implies that the gene replicated itself, inserting itself in multiple locations in the plasmid as it has the self-replicating capacity (Vandecraen et al., 2017). This movement is made possible by the existence of insertion sequences leading to possibly new genetic diversity through subsequent mutation and recombination. 

Question 4 

The NDM gene is located on self-transmissible plasmids that as have been shown also carry other antibiotic resistance genes. They have a high prevalence in hospital setups posing a huge challenge due to their horizontal gene transfer mechanism. The nursing staff remained the only contact between patient 1 and 2, meaning they were most likely the conduit of spread. The fact that it possesses a high rate of transfer to unrelated bacteria species makes it easily spread. The NDM positive bacteria have been commonly found to colonize the gastrointestinal tract, as evidenced in the rectal swab of patient 2 (Vandecraen et al., 2017). This means it could have been spread through the fecal-oral transmission route either through contaminated medications, food, hands or water handled by the nursing staff to patient 2. The circuit becomes complete as the patient also had Klebsiella one of the bacteria that express NDM. Besides, the bacteria may have survived on surfaces such as iv poles and beds that may have been a common point of contact between the two patients. 

References 

Heinz, E. (2019). Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1. Nature . Retrieved from https://www.nature.com/articles/s41598-019-38943-7 

Navon-Venezia, S., Kondyatreva, K., & Carattoli, A. (2017). Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS MICROBIOLOGY REVIEWS, 41 (3), 252-275. Retrieved from https://academic.oup.com/femsre/article/41/3/252/3830265 

Reygaert, W. C. (2018). An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiology . Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604941/ 

Vandecraen, J., Chandler, M., Aertsen, A., & Van Houdt, R. (2017). The impact of insertion sequences on bacterial genome plasticity and adaptability. Critical Reviews in Microbiology . Retrieved from https://www.tandfonline.com/doi/full/10.1080/1040841X.2017.1303661