Harnessing the effect of iron deprivation to attenuate the growth of opportunistic pathogen <i>Acinetobacter baumannii</i>
<i>Acinetobacter baumannii</i> is an opportunistic pathogen having high infectivity among immunocompromised patients. The bacteria are resistant to major first-line antibiotics and have become a serious concern in the aspect of nosocomial and community-acquired infections. To overcome this dire situation, the necessity of introducing new approaches is undeniable, which can bypass the need for conventional antibiotic therapy. In this article, we have pinpointed the importance of iron in <i>A. baumannii.</i> Iron is an essential micronutrient in all bacteria. Loss of iron acquisition leads to membrane destabilization, and change in the expression of iron-transporting or -metabolizing genes causes death of the bacteria. Iron scavenging was primarily mediated by different chelators, and β-thujaplicin showed the best antibacterial efficacy with respect to time killing assay and CFU analysis. When iron (Fe<i><sup>2+</sup></i>) was supplemented after initial deficiency, the growth of the bacteria was seen to be restored. Iron deprivation also disintegrates the biofilm matrix, a major cause of bacterial resistance against different types of antibiotics. Moreover, iron scavenging promotes inhibition of biofilm sessile persister cells, the root cause of recalcitrant and chronic infection. As a part of antimicrobial therapy, β-thujaplicin was treated alongside colistin and chloramphenicol at an amount significantly lower than its MIC value. Our results indicated that β-thujaplicin nicely complemented those antibiotics to potentiate their antimicrobial action. In a nutshell, iron chelating agents are potential alternative therapeutics that can be used alongside different antibiotics to circumvent the resistance of different nosocomial pathogens.
Authors
- Sukhendu Mandal (ORCID: https://orcid.org/0000-0002-7752-0982)
- Kunal Sikder (ORCID: https://orcid.org/0000-0002-4235-0936)
- Ali Hossain Khan (ORCID: https://orcid.org/0000-0001-7155-0200)
- Dipak Manna (ORCID: https://orcid.org/0000-0001-5112-3957)
- Arnab Basu (ORCID: https://orcid.org/0000-0002-8048-8733)
- Amit Ranjan Maity (ORCID: https://orcid.org/0000-0002-5253-3680)
- Soumyananda Chakraborti (ORCID: https://orcid.org/0000-0002-7384-690X)
- Shyamal K. Saha (ORCID: https://orcid.org/0000-0003-4977-2928)
- Debasrita RoyChowdhury
Institutions
- Ramakrishna Mission Vivekananda Educational and Research Institute (IN)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Birla Institute of Technology and Science - Hyderabad Campus (IN)
- S.N. Bose National Centre for Basic Sciences (IN)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1128/aac.01689-24
- Citations
- 4
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 2.36