Intracellularly driven chemical modifications of antimicrobial secondary metabolites: Potent mechanisms of self-resistance

Abstract

Natural products (NPs), especially antibiotics, exhibit diverse bioactivities and often play critically important roles in dictating and/or driving medical, health, agricultural, animal husbandry, and cosmetic industry initiatives. An important realization in the field of NP applications is that both targeted pathogens and the antibiotic-producing hosts themselves have usually evolved a host of resistance strategies by which to protect themselves. Although the former class of microbes (pathogens) has come to be associated with the global antibiotic resistance crisis, mechanisms by which producing organisms become resistant or tolerant to the ill effects of their bioactive metabolites have begun to attract a great deal of attention. Studies aimed at understanding antibiotic resistance have shown that producer-bourne mechanisms of self-resistance are possible prototypes by which to understand corresponding resistance elements in antibiotic-resistant bacteria. Historically speaking, the most efficient and potent chemistries employed by pathogens to evade harm from antimicrobial NPs have evoked enzymatically-driven transformations. We summarize herein the primary chemical modifications known to impart upon bioactive NP-producing microbes a means of self-defense against their own antimicrobial secondary metabolites; in understanding these chemistries we expect to gain new insights into how antibiotic resistance mechanisms in targeted pathogens might be circumvented or prevented. Such a translation of knowledge has a high likelihood of advancing humanity's ability to counter drug-resistant pathogens.

Keywords

Natural products / Self-resistance / Chemical modifications / Antibiotic resistance / Self-defense / Chemical inactivation

Author contribution statement

Xiaohua Li: performed literature research, drafted the paper, and revised the review. Jianhua Ju: initiated and supervised the work, and provided insights.

Both authors have read and approved the final manuscript.

Data availability

Not applicable.

Ethics approval

Not applicable.

Funding information

Related research work in our group was supported by the National Natural Science Foundation of China (22037006, U2106207), Key Science and Technology Project of Hainan Province (ZDKJ202018), Local Innovation and Entrepreneurship Team Project of Guangdong (2019BT02Y262), Open Program of Shen Zhen Bay Laboratory (SZBL2021080601006).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We thank Professor Runping Fang and Professor Weilong Liu from Shandong University for their help in revising the manuscript.

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