Insights into the Variation in Bioactivities of Closely Related Streptomyces Strains from
Marine Sediments of the Visayan Sea against ESKAPE and Ovarian Cancer
CRITIQUE PAPER
Synopsis:
According to Edna M. Sabido et al., worldwide public health is increasingly at risk
from antimicrobial drug resistance.The 'ESKAPE' species (Enterococcus faecium,
Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas
aeruginosa, and Enterobacter spp.) exhibit multidrug resistance. This is especially concerning
as they are the source of several deadly illnesses in medical facilities. There is a pressing need
for novel antibiotic scaffolds, even though several promising drugs are being developed.
Researchers studying antibacterial agents, however, have had difficulty finding novel small
compounds with significant cellular activity—particularly those that work against Gram-
negative bacteria that are resistant to many drugs. This challenge eventually results from a
lack of knowledge regarding chemical penetration via bacterial membranes and export
mechanisms. This opinion piece highlights the results of target-based and phenotypic
screening efforts conducted at AstraZeneca over the previous ten years, talks about some of
the chemistry-related difficulties that arose, and ends with a description of novel strategies
that combine sophisticated biological tools and computational modeling to potentially find
new antibacterial agents.
Main Arguments:
1. Marine Sediments: A Rich Reservoir of Bioactive Actinomycetes
2. Genetic and Metabolic Diversity Drive Bioactivity Variation
3. Implications for Natural Product Discovery and Drug Development
Marine sediments, particularly from unexplored regions like the Visayan Sea in the
Philippines, represent a largely untapped resource for discovering novel bioactive
compounds. Actinomycetes, such as the Streptomyces species identified in this study, thrive
in these environments and have evolved to produce a diverse array of secondary metabolites.
These compounds exhibit potent bioactivities against a broad spectrum of pathogens,
including the notorious ESKAPE pathogens and cancer cells. By isolating and characterizing
actinomycetes from marine sediments, we unlock the potential for discovering new
antibiotics and anticancer agents, thereby addressing the pressing global health challenges
posed by infectious diseases and cancer.
The observed variation in antibiotic and anticancer activities among phylogenetically
identical Streptomyces strains underscores the complexity of natural product biosynthesis and
regulation. Despite sharing identical 16S rRNA gene sequences, these strains harbor diverse
biosynthetic gene clusters (BGCs), including type I and II polyketide synthase (PKS) and
non-ribosomal peptide synthetase (NRPS) genes. This genetic diversity gives rise to distinct
metabolite profiles, comprising both core and strain-specific compounds. Consequently, the
bioactivity exhibited by each strain is not solely dictated by the presence of specific BGCs
but also influenced by the intricate interplay of metabolic pathways and environmental
