Antibiotic Resistance in Poultry Industry: Mechanisms of Resistance

Antibiotics target microbial cells, inhibiting growth or causing cell death by destroying cell walls or membranes, disrupting protein and nucleic acid synthesis, or interfering with metabolic pathways. Examples include aminoglycosides, tetracycline, and macrolides for cell-wall targeting, and rifampin and fluoroquinolones for protein and nucleic acid synthesis. Others like daptomycin and sulfonamides disrupt metabolic pathways and membrane integrity. Antibiotic resistance evolves, affecting bacterial physiology and even conferring resistance to unrelated compounds. Some resistance mechanisms remain unknown, suggesting hidden factors influencing antibiotic resistance.

We have used antimicrobials in the poultry industry for disease treatment and as AGP’s for many years to keep the flock healthy and improve liveability of birds and the overall poultry production. But, many studies give us the information that overuse or underdosing or use of single antibiotic so long directed towards the AMR in poultry. So, we need to know, what Is AMR? How is it developed by microbes?

In our previous article we talked about the history and background of antibiotic resistance in the poultry industry and in this article we will be focusing on the different mechanisms by which the important bacteria develop resistance.

Genetic Mutations

Antimicrobial resistance emerges from genetic mutations encoded on bacterial chromosomes, evolving against antibiotics and passing on to subsequent generations. Mutations arise naturally, such as during cell division when DNA is copied imperfectly, introducing small differences from the original sequence.

Mutation of Target Sites

• Mutations affect antibiotic effectiveness in two main ways:
• Altering target sites of antibiotics:
  • Changes in enzymes or bacterial ribosomes.
  • Altered structure of binding site makes it less attractive to antibiotics.
  • Antibiotics become less effective, leading to resistance.
• Increasing activity of efflux pumps:
  • Proteins expel antibiotics from bacterial cells before they work.
  • Example: mutations in RNA polymerase gene of Mycobacterium tuberculosis.
  • Mutations change binding sites, reducing effectiveness of antibiotics like rifampicin in inhibiting RNA synthesis.

Epigenetic Mechanism

• Initial observation of antibiotic resistance gene emergence and transmission:
  • Observed in isolated strains of Escherichia coli.
  • Strains exposed to varying concentrations of antibiotics like tetracycline, nalidixic acid, and ampicillin.
• Study findings:
  • Utilized data from de novo assembly of short-read sequences.
  • Combined with a metagenomic approach.
  • Suggested lateral transfer of antibiotic resistance genes.
  • Mobilization of modified sequences among clinical pathogens from soil bacteria in the environmental reservoir.
• Questioning efficacy of random uncontrolled evolution:
  • Proposed acquisition of antibiotic resistance genes through epigenetic mechanisms.
  • Stemming from maintenance of specific chromatin configurations or DNA methylation states.
  • High rate of reversal of resistant phenotypes supports the idea of epigenetic mechanisms.
  • Epigenetic mechanisms do not confer lasting phenotype.

Horizontal Gene Transfer

• Horizontal gene transfer (HGT) is significant for:
  • Spread, evolution, and maintenance of antibiotic resistance in pathogenic bacteria.
  • Elimination of antibiotic resistance genes (ARGs) from natural environments in clinical settings.
• Example: Dissemination of carbapenem resistance in Enterobacteriaceae:
  • blaNDM-1 gene encoding carbapenemase enzyme spreads rapidly through HGT.
  • Identified in various Enterobacteriaceae species, enabling resistance to carbapenem antibiotics.
  • Contributes to broad resistance to last-resort antibiotics.
• Example: Shigella outbreak in the United Kingdom:
  • Transfer of plasmid-borne antibiotic resistance gene.
  • Plasmid carries resistance to azithromycin.
  • Facilitates proliferation of previously rare pathogens, reducing efficacy of conventional antibiotics.
  • Multiple outbreaks involving distinct strains emerge as strains acquire the same plasmid independently.

Conjugation

• Primary mechanism of horizontal gene transfer (HGT).
• DNA transferred between cells via pili or adhesins.
• Facilitated by conjugative machinery on plasmids or integrative conjugative elements.

Transformation and Transduction

• Transformation: Uptake of genetic material from the environment.
• Transduction: Introduction of foreign DNA via viruses.
• Transformation facilitated by factors like growth phase or specific substances.

Biofilm Formation

• Bacteria’s resistance is influenced by metabolic state.
• Biofilms: Organized communities with self-produced matrix.
• Biofilm shields bacteria from antibiotics and the immune system.
• Quorum sensing coordinates resistance mechanisms.
• Biofilms serve as focal points for transmission of antibiotic resistance genes.

Stringent Response

• (p) ppGpp modulation regulates bacterial responses to stress.
• Prioritizes survival over growth.
• Downregulates growth-related genes.
• Activates stress adaptation mechanisms like efflux pumps.

Enzymatic Inactivation

• Bacteria possess enzymes that modify or degrade antibiotics.
• Example: β-lactamase breaks down β-lactam antibiotics.

Efflux Pumps

• Membrane proteins actively remove antibiotics from cells.
• Leads to multidrug resistance.
• Example: Pseudomonas aeruginosa employs efflux pumps like MexAB-OprM.

Alternative Metabolic Pathways

• Bacteria utilize alternative pathways to evade antibiotic effects.
• Nullifies antibiotic effectiveness against specific targets.

Altered Permeability

• Changes in cell membrane permeability impact antibiotic entry.
• Decreased permeability limits antibiotic uptake.
• Example: Gram-negative bacteria reduce outer membrane permeability to resist tetracycline.

Conclusion

• Different mechanisms of developing resistance for antibiotics have been studied
• Development of resistance patterns is influenced by the exposure of antibiotics Hence; we need to understand the mechanism of action of different classes of antibiotics we use in poultry.
• A bacteria can develop more than one mechanism of resistance, which is further termed as multidrug resistance.
• Understanding the resistance mechanisms can help us to select different alternatives for antibiotics
• Antibiotic resistance and its threat compels us to question our future approach.