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

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Antimicrobial Resistance

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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.

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Abbreviations

AHLs:

Acyl-homoserine lactones

AMR:

Antimicrobial resistance

BAM:

β-barrel assembly machinery

BLIs:

β-lactamase inhibitors

CDC:

Centers for Disease Control and Prevention

CRE:

Carbapenem-resistant Enterobacteriaceae

Da:

Dalton

EPIs:

Efflux pump inhibitors

EPS:

Extracellular polymeric substances

ESBL:

Extended-spectrum β-lactamase

FDA:

Food and Drug Administration

g:

Grams

h:

Hour

IC50:

Half-maximal inhibitory concentration

ICU:

Intensive care unit

LD50:

Lethal dose, 50%

LPS:

Lipopolysaccharides

M.S.:

Mass spectrometry

MBC:

Minimum bactericidal concentration

mcr :

Mobilized colistin-resistant gene

MDR:

Multiple drug resistant

MIC:

Minimum inhibitory concentration

mM:

Millimolar

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

MW:

Molecular weight

NMR:

Nuclear magnetic resonance

NRP(s):

Nonribosomal peptide(s)

NRPS:

Nonribosomal peptide synthetases

OM:

Outer membrane

PK:

Pharmacokinetics

PABA:

Para-aminobenzoic acid

PD:

Pharmacodynamics

PDR:

Pan drug resistant

PNBA:

Para-nitrobenzoic acid

QS:

Quorum sensing

QSIs:

Quorum sensing inhibitors

RBCs:

Red blood cells

Ripp(s):

Ribosomally synthesized and posttranslationally modified peptide(s)

RMAs:

Resistance modifying agents

RND:

Resistance nodulation and cell division

SAR:

Structure-activity relationship

WHO:

World Health Organization

XDR:

Extensively drug resistant

μg:

Microgram

μl:

Microliter

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Authors and Affiliations

  1. Clinical Microbiology and Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India

    Manoj Jangra, Parminder Kaur, Rushikesh Tambat, Vrushali Raka, Nisha Mahey, Nishtha Chandal, Shobit Attery, Vikas Pathania, Vidhu Singh & Hemraj Nandanwar

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  1. Manoj Jangra
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  2. Parminder Kaur
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  3. Rushikesh Tambat
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  4. Vrushali Raka
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  5. Nisha Mahey
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  6. Nishtha Chandal
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  7. Shobit Attery
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  8. Vikas Pathania
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  9. Vidhu Singh
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  10. Hemraj Nandanwar
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Correspondence to Hemraj Nandanwar .

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Editors and Affiliations

  1. Department of Biotechnology, Savitribai Phule Pune University, Modern College of Arts, Science and Commerce, Ganeshkhind, Maharashtra, India

    Vinay Kumar

  2. Department of Botany, Savitribai Phule Pune University, Ramkrishna More Arts, Commerce and Science College, Pune, Maharashtra, India

    Varsha Shriram

  3. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India

    Atish Paul

  4. School of Biomedical Sciences, Mahatma Gandhi Mission Institute of Heal, Navi Mumbai, Maharashtra, India

    Mansee Thakur

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Jangra, M. et al. (2022). Recent Updates on Bacterial Secondary Metabolites to Overcome Antibiotic Resistance in Gram-Negative Superbugs: Encouragement or Discontinuation?. In: Kumar, V., Shriram, V., Paul, A., Thakur, M. (eds) Antimicrobial Resistance. Springer, Singapore. https://doi.org/10.1007/978-981-16-3120-7_14

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