Recent Updates on Bacterial Secondary Metabolites to Overcome Antibiotic Resistance in Gram-Negative Superbugs: Encouragement or Discontinuation?

ABSTRACT

The rapid spread of COVID-19 has dramatically changed our perspective about how we should be well prepared for upcoming health disasters in the future. Like COVID-19, the world does not seem prepared to fight the slow-moving pandemic, i.e., antimicrobial resistance (AMR). At present, more than 7, 00, 000 people per year across the globe succumb to drug-resistant infections. According to several reports, if we fail to respond, AMR could lead to the loss of ten million lives and trillions of money by 2050. Among the different pathogens affecting human health, the World Health Organization (WHO) has recently announced a priority list of drug-resistant bacteria to pave the way for the development of new antibiotics. Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most notorious ones and are responsible for the majority of healthcare-associated infections. These pathogens come under the critical threat category because they express resistance to all of the current antibiotics. The modern combinatorial chemistry approaches and chemical genomics have been unsuccessful to provide enough new antibiotics. In stark contrast to this, natural products have been gifted with remarkable chemical diversity and biological activity. Our modern antibiotic armamentarium was built from microbes' natural products, especially Streptomyces spp. and Bacillus spp. isolated in the golden era. Today, the antibiotic discovery pipeline has almost dried up, in part due to the rediscovery of already known compounds from bacteria, and no new classes emerged from bacteria until recently. These novel natural antibacterial agents from bacteria resurged a spark in the exploitation of bacteria to find new chemical entities. This chapter mainly focuses on natural antimicrobials and adjuvants isolated from the bacterial domain in the last two decades, i.e., from 2001 to 2020, and their status to fight drug-resistant Gram-negative superbugs. We have also described briefly the discovery of synthetic compounds based on natural scaffolds. In conclusion, the bacterial natural products comprise a goldmine to fight superbugs, and future research should be focused on exploring new antimicrobials from bacterial diversity. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.