The resistance of microorganisms is connected with ability of fast replication and adaption ability based on plasmid DNA.

Any how microorganisms will find a way to survive otherwise it will be end of life.

Microorganisms gain resistance as a result mutations, that may have occurred within the amino acid sequence.

In my opinion, by the different factors (environment, habit or practice, link between cells (recognition) etc). Because once all these bills have been recognized by the body; it will be difficult for the antibiotic to be effective against the pathogens previously recognized.

Microorganisms gain resistance to antimicrobial agents through various mechanisms, which can be broadly categorized into genetic and biochemical processes. Here’s how they do it:

1. Genetic Mechanisms

Mutation: Spontaneous changes in the microorganism's DNA can alter target sites for antibiotics, making the drug ineffective.

Horizontal Gene Transfer (HGT):

Conjugation: Transfer of resistance genes via plasmids through direct contact between bacteria.

Transformation: Uptake of free DNA fragments (including resistance genes) from the environment.

Transduction: Transfer of resistance genes via bacteriophages (viruses that infect bacteria).

2. Biochemical Mechanisms

Enzymatic Inactivation: Microorganisms produce enzymes that destroy or modify the antibiotic. For example:

Beta-lactamase breaks down beta-lactam antibiotics like penicillins.

Efflux Pumps: Active pumping of the antibiotic out of the cell to maintain low intracellular concentrations.

Alteration of Target Sites: Modifications in the antibiotic’s binding site (e.g., ribosomes, enzymes) prevent the drug from acting.

Bypass Pathways: Microorganisms develop alternative pathways to bypass the metabolic process inhibited by the antibiotic.

Reduced Permeability: Alteration in the cell wall or membrane reduces drug entry into the cell.

3. Environmental and Behavioral Factors

Overuse and Misuse of Antibiotics: Excessive or inappropriate antibiotic use in healthcare, agriculture, and self-medication promotes resistance.

Incomplete Treatment: Not completing prescribed antibiotic courses allows some microorganisms to survive and adapt.

Biofilm Formation: Microorganisms in biofilms are more resistant due to their protective environment and limited drug penetration.

There is an important mechanism that is not included in this list, which is impermeabilization. Numerous molecules, including many antibiotics, penetrate bacteria through specific hydrophilic channels opened in the Gram-negative wall, defined by a group of proteins known generically as porins. The decrease in the number of these porins, mutations in them or their substitution by others of different characteristics, reduce or hinder the penetration of the antibiotic through the bacterial wall, so that it does not reach a sufficient intrabacterial concentration to act on its target with sufficient potency.

Dear Juan Luis Muñoz Bellido,

Thank you so much.

Sincerely,

However, due to selective pressure, bacteria can develop resistance through mutations in the porin gene.[5] The mutations may lead to a loss of porins, resulting in the antibiotics having a lower permeability or being completely excluded from transport. These changes have contributed to the global emergence of antibiotic resistance, and an increase in mortality rates from infections.[5]

https://en.wikipedia.org/wiki/Porin_(protein)

Selection Pressure (3rd)

Microbes gain resistance through genetic mutations/acquiring resistance genes via horizontal gene transfer (transformation, transduction, conjugation). The changes alter drug targets, increase efflux/reduce uptake. Antibiotic misuse creates selective pressure, enabling resistant strains to survive, multiply and spread complicating infection treatment and control.

لكي تحصل الكائنات الحية الدقيقة على مقاومة، فإن عملية اكتساب المقاومة تعتمد بشكل أساسي على التطور الجيني. عندما تتعرض الكائنات الحية الدقيقة لظروف بيئية قاسية أو لعوامل تحفيزية معينة، قد تحدث تغييرات جينية تسمح لها بالتكيف مع هذه الظروف. يمكن أن يحدث ذلك من خلال عملية تحور الجينات أو من خلال تبادل الجينات مع غيرها من الكائنات.

على سبيل المثال، في حالة البكتيريا، قد تكسب البكتيريا مقاومة للمضادات الحيوية نتيجة لتحور في الجينات التي تجعلها تقاوم تأثير المضادات الحيوية. هذا التحور الذي يؤدي إلى المقاومة يمكن أن ينتقل بين البكتيريا بسرعة عن طريق عملية الانتقال الجيني.

بشكل عام، عملية اكتساب المقاومة لدى الكائنات الحية الدقيقة تعتمد على التطور الجيني وقدرتها على التكيف مع الظروف المتغيرة.

The resistance traits either vertically transmitted via mutation or transmitted horizontally through conjugation, transformation,transduction or transposition but the mechanisms by which bacteria resist antibiotics might be Enzyme production, porins mutations, change the binding sites, metabolites modulation, biofilm and efflux pumps