What are the origins of growing microbial resistance? Both Lamarck and Darwin were right

ABSTRACT

Introduction

Microorganisms of clinical importance frequently develop resistance to drug therapy, now a growing problem. The experience with Mycobacterium tuberculosis is a representative example of increasing multi-drug resistance. To avoid reaching a crisis in which patients could be left without adequate treatment, a new strategy is needed. Anti-microbial therapy has historically targeted the mechanisms rather than origin of drug resistance, thus allowing microorganisms to adapt and survive.

Areas covered

This contribution analyses the historical development (1943–2020) of the evolution of multi-drug resistance by M. tuberculosis strains in light of Darwin’s and Lamarck’s theories of evolution.

Expert opinion

Regarding the molecular origin of microbial drug resistance, genetic mutations and epigenetic modifications are known to participate. The analysis of the history of drug resistance by M. tuberculosis evidences a gradual development of resistance to some antibiotics, undoubtedly due to random mutations together with natural selection based on environmental pressures (e.g., antibiotics), representing Darwin’s idea. More rapid adaptation of M. tuberculosis to new antibiotic treatments has also occurred, probably because of heritable acquired characteristics, evidencing Lamarck’s proposal. Therefore, microbial infections should be treated with an antibiotic producing null or low mutagenic activity along with a resistance inhibitor, preferably in a single medication.

KEYWORDS:

• Antibiotics
• genetics
• infection
• lamarck
• darwin
• mutations
• drug resistance
• mycobacterium tuberculosis

Article highlights

• Historically, drug resistance by M. tuberculosis stems from both random mutations and heritable acquired characteristics.

• New treatment regimens should include an antibiotic with null or low mutagenic activity and a resistance inhibitor, preferable in one molecule.

• Some first and second line anti-tuberculous drugs have mutagenic potential.

• Drug resistance should be addressed at its origin, not by interrupting the metabolic and/or structural processes of microorganisms.

• Since there is no conclusive explanation for the molecular origin of drug resistance, theories of evolution should be consulted.

Acknowledgments

The authors would like to give thanks to Bruce Allan Larsen for proofreading the manuscript.

Declaration of interest

J. A. Guevara-Salazar is a member of the EDI fellowship program of the IPN. J. G. Trujillo Ferrara is a member of the COFAA and EDI fellowship programs of the IPN. The authors have no other relevant affiliations or financial involvement with any organization or entity that could have a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultants, expert testimony, professional fees, ownership of stock or stock options, grants or patents received or pending, and royalties.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Consejo Nacional de Ciencia y Tecnología (CONACyT, grant # 257364) and the SIP Project of the Instituto Politécnico Nacional (grants # 20181505 and 20196701). J. R. Morán-Díaz thanks the Consejo Nacional de Ciencia y Tecnología (CONACyT, grant # 704263) for the National Scholarship received and the program of the Beca de Estímulo Institucional de Formación de Investigadores (BEIFI, grant # 2018, registration 324 and 292) for additional support.