Growth inhibition of Acinetobacter by 5-chloro-indole-3-acetic acid

Abstract

The Acinetobacter calcoaceticus-baumannii complex includes high-priority, multidrug-resistant pathogens for which novel antibiotics are urgently needed. Many bacterial strains from this complex harbor a so-called iac gene cluster that codes for the catabolism of indole-3-acetic acid (IAA). Here, we demonstrate that possession and expression of iac genes represent an Achilles' heel for Acinetobacter species, which can be exploited to suppress bacterial growth by treatment with IAA and its analog 5-chloro-IAA.IMPORTANCEAcinetobacter baumannii is a deadly bacterial pathogen and one of the leading causes of hospital-acquired infections worldwide. It is also known for its resistance to many antibiotics currently available. In this study, we show that Acinetobacter bacteria choke on a mixture of IAA and 5-chloro-IAA, offering a path to the discovery and development of a novel drug treatment.

Keywords: Acb complex; Acinetobacter baumannii; Acinetobacter lactucae; ESKAPE.

Fig 1

Alignment of iac gene neighborhoods from A. lactucae NRRL B-41902 (top) and A. baumannii ATCC 19606 (bottom). To generate this figure, the genomes of the two strains were retrieved as .gbff files from NCBI using accession numbers NZ_LRPE01000009.1 and NZ_CP046654.1, respectively, and aligned in clinker (23). Individual genes are labeled with their RefSeq locus tag. Gray ribbons connect orthologous genes; the number that is displayed on each ribbon refers to the percentage of amino acid identity shared between the predicted proteins of each gene pair. The dashed rectangle marks the iac gene cluster (iacR-iacHABICDEFG).

Fig 2

Growth of A. lactucae NRRL B-41902 on M9 minimal medium with added trace elements (Panke et al. [24]) and supplemented with either 1 mM IAA (black circles, A, B and C), with 1 mM 5-CI-IAA (white circles, A) or with a mixture of IAA and 5-Cl-IAA (gray circles), where 5-Cl-IAA was added either at the same time as IAA (B) or with a 6-h delay (C). Cells were inoculated from an overnight, washed culture on King’s Medium B Broth and incubated while shaking at 28°C. The optical density at 600 nm (OD₆₀₀) was measured in a GENESYS 50 spectrophotometer (Thermo Fisher). IAA and 5-Cl-IAA were sourced from Biosynth International. Shown are the averages of three replicated experiments, with the bars representing the standard error.