INTRODUCTION
Predictive modelling is a computational and statistical technique used to
forecast future outcomes based on current or historical data. In the field of
microbiology, it offers a powerful tool to anticipate the emergence and
development of antimicrobial resistance (AMR), allowing proactive clinical
and public health responses. According to Caballero and Poon, "predictive
modelling in microbial genomics offers an invaluable framework to anticipate
the emergence of resistance and guide therapeutic strategies in real time"
(1).
Unlike conventional diagnostic techniques that detect resistance after it has
emerged, predictive modelling enables early forecasting, making it more
valuable for prevention and control strategies. Ventola notes that “delayed
detection of resistant infections contributes to increased morbidity,
mortality, and healthcare costs” (2). This justifies the shift toward
anticipatory models in modern infectious disease management.
This study focuses on Pseudomonas aeruginosa, a Gram-negative bacterium
well-known for its resistance to multiple antibiotics. It has been classified by
the World Health Organization as a critical priority pathogen due to its
capacity to cause severe hospital-acquired infections and its increasing
resistance to available treatment options (3). In particular, this study
investigates antibiotic-induced mutations in the chromosomal AmpC β-
lactamase gene, which is a key driver of resistance in P. aeruginosa.
The AmpC gene, when overexpressed or mutated, enables the organism to
resist β-lactam antibiotics, especially cephalosporins. Jacoby emphasizes that
“mutations in the regulatory regions of ampC or changes in the expression of
AmpR can cause hyperproduction of AmpC, leading to high-level resistance”
(4). Therefore, this gene is a valuable target for predictive modelling of AMR
development.
P. aeruginosa was chosen for this study due to its high clinical relevance,
well-documented resistance mechanisms, and the global threat it poses.
Moreover, findings from this model may extend to other related pathogens
such as Enterobacter spp., Citrobacter freundii, and Serratia marcescens,
which share similar chromosomal resistance mechanisms (5).Through the
development of this predictive model, the study aims to contribute to a
better understanding of mutation-driven resistance and offer a framework for
anticipating and combating AMR in critical pathogens.
References
1. Caballero JD, Poon AF. Predictive modelling in microbial genomics:
Challenges and opportunities. Front Genet. 2021;12:647254.
doi:10.3389/fgene.2021.647254
2. Ventola CL. The antibiotic resistance crisis: Part 1: Causes and threats. PT.
2015;40(4):277–83. PMID: 25859123
3. World Health Organization. Global priority list of antibiotic-resistant
bacteria to guide research, discovery, and development of new antibiotics.
Geneva: WHO; 2017. Available from:
https://www.who.int/publications/i/item/WHO-EMP-IAU-2017.12
4. Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev. 2009;22(1):161–82.
doi:10.1128/CMR.00036-08
5. Livermore DM. Multiple mechanisms of antimicrobial resistance in
Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis.
2002;34(5):634–40. doi:10.1086/3387