Mechanism of acquired resistance transmission:

It may develop through mutation or gene transfer.

1. Mutation:

• occurs due to insertion, deletion or substitution off one or more nucleotides in genome which may be present on chromosomes or on extra-chromosomal materials called plasmids.
• Resistance by mutation occurs either in single step or series of step:

Single step mutation:

• Bacterial resistance develops in single step due to mutation occuring in powerful gene.
• Emerges rapidly and confers (grant) high degree of resistance.
• Ex: Resistance of enterococci to streptomycin and staphylococci to rifampicin developed in single step mutation.

Multiple step mutation:

• Bacterial resistance develops in multiple steps due to mutation occuring in number of different genes.
• Develop slowly and gradually and confers slight resistance.
• Ex: development of resistance to erythromycin, tetracyclines & chloramphenicol occur in multistep mutation.

2. Gene transfer:

• Resistance by gene transfer develops by the transfer of genetic material coding for resistance (R factor) from resistant microorganism to susceptible microorganism
• Occurs through transduction, transformation, & conjugation.
• When an organism incorporates genetic material from another organism without being offspring of that organism is called horizontal gene transfer (HGT) or lateral gene transfer (LGT).

I. Transduction:

• Process by which R factor is transferred from AMA resistant bacterium to AMA susceptible bacteria by bacteriophage or phage.
• Bacteriophage utilise bacterial machinery of AMA resistant bacterium for multiplication and during process incorporate R factor into genetic material of viral progeny

When viral progeny infect other bacteria, R factor is passed onto new bacteria

New bacteria becomes resistant to drug and contribute to pass on resistance to their progeny.

• Less common method by which organism acquire resistance
• Involved in transfer of resistance in staphylococcus aureus and streptococci to penicillin by inducing penicillinase production.

II. Transformation:

• Process of genetic alteration of cell resulting from direct uptake, incorporation and expression of exogenous genetic material from its surrounding
• In this process resistant bacteria release free or naked DNA consisting of R factor

Such gene are incorporated by susceptible bacteria from surrounding and take up through cell membrane

Susceptible bacteria becomes resistant after gene uptake

• Occurs less
• Pneumococci & Neisseria have acquired resistance to penicillin by transformation.
• Conjugation:
• Here R factor is transferred from resistant bacterium to susceptible bacterium by direct contact through pilus or bridge.
• Formation of pilus is coded by resistance transfer factor (RTF) or plasmid.
• Most important mechanism for spread of antimicrobial drug resistance.
• Recipient and donor belong to different species, different genera, and pathogenic & non-pathogenic.
• Common in members of enterobacteriaceae, pseudomonas species & anaerobes of intestinal tract.
• Ex: Streptomycin resistance to E.coli, Penicillin resistance to Haemophilus & Chloramphenicol resistance to typhoid bacilli