Antimicrobial Resistance: An Urgent Public Health Crisis
Abiola Isawumi (PhD)
West African Centre for Cell Biology of Infectious Pathogens
University of Ghana
Antimicrobial Resistance: An Urgent Public Health Crisis
The human race has persevered on the planet for millions of years and have become more adapted to its existing environment; however, bacteria have existed a little longer. Bacteria are small, but can colonize and survive in every habitable environment including hostile and extreme ecological niche and conditions1. They could be air or water-borne, terrestrial, and also cohabit in beneficial or parasitic relationships. Also, some have developed mechanisms to circumvent various host defenses to initiate infections2. Others take advantage of exposed anatomical surfaces to facilitate host-microbe interactions, which in turn influences immune systems’ reactions (to antigens, pathogens and associated virulence factors)1. Some of the gut microbiota produces specialized antimicrobials that boost the activities of immune factors3.
AMR – Global Public Health Crisis
Majority of these antimicrobials function by impairing crucial bacterial functions like replication, protein and cell wall synthesis among others. Based on their mode of action, antimicrobials could be bactericidal or bacteriostatic. However, most public health crisis has been associated with certain Gram-negative bacteria resisting this mode of action, especially Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii 4. These bacteria constitute a global threat as antimicrobial resistance (AMR) pathogens defiling all recommended treatment methods; making AMR a significant public health problem that demands urgent attention.
Bacteria War Against Antimicrobials
Overuse and misuse of antimicrobials resulting in selection pressure is assumed the primary cause of resistance development5. Some bacteria produce enzymes that break down the chemical structure of antibiotics, while others alter their targets, modifies surface membrane lipid A, use eDNA for antibiotics sequestration and disrupts lipocalins. Others use extra genetic material (plasmids) inherited from the environment and specialized pumps to extrude antibiotics from their cells. Some are tolerant and persist in the presence of antibiotics; form spores, capsules, cell-aggregates and extra cellular matrix such as biofilms that inhibit antibiotic penetration. These resistance mechanisms are not all-inclusive; progressive research in the field of AMR are uncovering others.
Bacteriophages and Anti-infective: A Glimpse of Hope
Despite the ravaging effects of AMR globally; there is however, some hope. The next generation of antimicrobial drugs should be specialized anti-infective agents. Also, specific viruses (bacteriophages) can be leveraged to eliminate resistant bacteria at the organismal level6. Bacteriophages have specialized structure that enables them to lyse and destroy the boundary membranes and walls of bacteria. The interaction of bacteriophage molecules with bacterial receptors, which mediates internalization, is the key source of specificity in this process. Interests in the use of phages particularly against bacteria (and other microorganisms) has increased recently as a result of laboratory investigations and successful clinical trials in people. Phages can be isolated from diverse sources including the soil, ocean, plants, or biological specimen (blood).
The development of safe anti-virulence targeting chemical agents7 can lessen the compounding challenges of AMR. These agents would exclusively target the particular pathogen factors causing pathogenesis. Microbes rarely live in isolation, thus the idea of developing novel drugs that are tailored to pathogens is taken into consideration. Recent findings from studies of the microbial communities associated with humans (using human cohorts or animal models) suggest that disruption of the steady-state human-microbiome interaction, particularly with antibiotics, alters the immune and metabolic phenotype of the human host and raises the risk of developing immune and metabolic conditions like inflammatory bowel diseases, diabetes, and obesity, among others8. Destroying only pathogenic bacteria in a community of commensals is therefore crucial for the next antimicrobial agent.
Bad Habits Against Bugs
I am optimistic about the development of better treatments in the recent future; however apprehensive about how bad habits of drug abuse and self-medications might bring us back to the pre-antibiotic age. In order to protect the few but potent antimicrobials we currently have (or will have) in our arsenal against infectious agents, it is of priority people become conscious of the threat posed by resistant pathogens and also adopt a stewardship mentality. Also, information about AMR should be widely and clearly communicated in straightforward language; and whenever possible, in common terms using people’s native tongue or other forms of art (docudrama, cartoons, etc).
In conclusion, the development of pathogen/virulence-specific antimicrobial drugs, leveraging bacteriophages, anti-infective agents, limiting antibiotic in agricultural and animal productions are of utmost significance in the fight against AMR. However, better stewardship for currently used antibiotics and those that will be discovered and developed in the near-future is required.
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