While detection and reaction to light sources is a well-known process in environmental organisms exposed to diurnal light cycling, light detection also affects the biological processes of human pathogens. The human pathogen Acinetobacter baumannii, a microbe associated with hospital-acquired infections, responds to light to become less susceptible to specific antibiotics. A new Journal of Bacteriology study explores some of the additional physiological changes that may explain the A. baumannii light response. The authors find that “light modulates global features of A. baumannii lifestyle,” including effects on metabolic pathway expression levels, antioxidant enzyme levels, antibiotic resistance and pathogenicity.
225 genes are modulated by BlsA in response to blue light exposure in A. baumannii. Source.
The authors took advantage of previous research demonstrating that A. baumannii detects light through its BlsA photoreceptor. The research team, led by first author Gabriella Müller and senior author Maria Alejandra Mussi, compared the gene expression pattern of a ΔblsA mutant to a wild-type strain when exposed to blue light. Overall, they identified 225 genes differentially regulated by BlsA as part of the light response (see figure, right).
Some of the light-regulated genes explain previously identified phenotypes. Light exposure decreases A. baumanii susceptibility to minocycline and tigecycline, which may be explained by the observed increase in efflux pump EmrAB expression after blue light exposure. These tetracycline-class compounds must remain intracellular for their bacteriostatic activity, and the bacterium can circumvent this activity by increasing secretion of these molecules to the extracellular space.
Light exposure increased production of bacterial catalase and type VI secretion system (T6SS) proteins. These systems may help the bacteria ward off not only the ill effects of light-generated reactive oxygen species (ROS) within the cell, but also ROS from an infected host; similarly, the T6SS may aid in A. baumannii competition or in virulence phenotypes. Light exposure decreased production of PAA catabolic pathway enzymes, which generate virulence compound precursors, showing that there’s still much to learn about virulence and virulence regulation in this organism.
Other identified light-regulated regulons were previously unknown in A. baumannii. Light induced expression of genes required for biosynthesis of trehalose and surfactant, two carbohydrates that can aid microbial survival in harsh conditions. Trehalose production is associated with temperature and osmotic stress resistance and contributes to A. baumannii pathogenesis.
A. baumannii has gene regulatory mechanisms that allow it to grow in either the absence or presence of light. Though the original environment for A. baumannii is unknown, its global gene regulation in the presence of light suggests adaptation to environments with light fluctuation. The effects on carbohydrate and lipid metabolism suggest sophisticated adjustments for these environmental lifestyle changes, which may explain the success of A. baumannii as a pathogen.
Characterizing the A. baumannii light responses help researchers understand the genetic systems required by the bacteria for environmental adaptation – and can also help researchers understand how to disregulate these systems for the benefit of human health. Carbapenem-resistant A. baumannii was included in the list of critical bacterial infections requiring new antimicrobial strategies, published in 2017 by the World Health Organization. A 2015 study found that blue light exposure reduces A. baumannii burden in a mouse model of burn infection. Understanding the mechanism of blue light application as a potential antibacterial therapy requires dissecting bacterial genetic regulation under normal conditions, which the new Journal of Bacteriology study begins to address.
Photo credit: A. baumannii on HEK agar