The antibiotic crisis: On the search for novel antibiotics and resistance mechanisms

Abstract

In the relentless battle for human health, the proliferation of antibiotic‐resistant bacteria has emerged as an impending catastrophe of unprecedented magnitude, potentially driving humanity towards the brink of an unparalleled healthcare crisis. The unyielding advance of antibiotic resistance looms as the foremost threat of the 21st century in clinical, agricultural and environmental arenas. Antibiotic resistance is projected to be the genesis of the next global pandemic, with grim estimations of tens of millions of lives lost annually by 2050. Amidst this impending calamity, our capacity to unearth novel antibiotics has languished, with the past four decades marred by a disheartening ‘antibiotic discovery void’. With nearly 80% of our current antibiotics originating from natural or semi‐synthetic sources, our responsibility is to cast our investigative nets into uncharted ecological niches teeming with microbial strife, the so‐called ‘microbial oases of interactions’. Within these oases of interactions, where microorganisms intensively compete for space and nutrients, a dynamic and ever‐evolving microbial ‘arms race’ is constantly in place. Such a continuous cycle of adaptation and counter‐adaptation is a fundamental aspect of microbial ecology and evolution, as well as the secrets to unique, undiscovered antibiotics, our last bastion against the relentless tide of resistance. In this context, it is imperative to invest in research to explore the competitive realms, like the plant rhizosphere, biological soil crusts, deep sea hydrothermal vents, marine snow and the most modern plastisphere, in which competitive interactions are at the base of the microorganisms' struggle for survival and dominance in their ecosystems: identify novel antibiotic by targeting microbial oases of interactions could represent a ‘missing piece of the puzzle’ in our fight against antibiotic resistance.

Phages produce persisters

“…Given the lack of novel antibiotics (Van Goethem et al., 2024 ) and the increasing mortality due to resistant bacterial infections, ~5 M deaths/year (Murray et al., 2022 ), interest is surging in the use of phages to combat infections (Strathdee et al., 2023 ). However, bacteria can mutate rapidly to undermine some phage therapies (Little et al., 2022 ; Murray et al., 2022 ) as well as utilize effective phage‐defence systems such as toxin/antitoxins (Pecota & Wood, 1996 ).…”