Study Uncovers How Mycoplasma genitalium Responds to Nutrient Deprivation

Mycoplasma genitalium is an emerging sexually transmitted pathogen which has displayed increasing resistance to antibiotic treatments. M genitalium prevalence ranges from .7% to 3.3% in the general population, and it is the most prevalent bacterial sexually transmitted infection in men who have sex with men who are living with HIV.

Experts from the Universitat Autónoma de Barcelona have published a study in Emerging Microbes & Infections demonstrating how M genitalium bacteria compete with host organism cells for essential metal nutrients.

Metal acquisition systems are key components that bacterial pathogens need to compete with hosts for limited cellular resources. Different bacteria develop strategies to acquire metals within hosts, but transcriptional regulators of the Ferric Uptake Regulator (FUR) are widespread in bacteria and control both acquisition and storage.

Understanding these processes is significant, as FUR inactivation can lead to attenuated virulence and colonization defects in bacteria such as Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus.

The investigators grew M genitalium strains in tissue culture flasks to conduct their experiments.

Cells were shocked with a metal chelator and transcription was compared to that of cells grown under routine culture conditions. Genome-wide RNA sequencing analysis allowed the team to investigate transcriptional changes in the bacteria following iron starvation.

There were more than 80 differentially expressed genes during metal starvation. Metal starvation led to a pronounced up-regulation of components in the bacteria which are important to maintaining protein integrity.

Transcript levels of genes involved in regulation of sugar transport and carbon metabolism also increased with metal depletion.

Conversely, the metal depletion led to inhibition of transcription of several genes related to carbohydrate metabolism. The investigators also observed decreased transcript levels of the ribulose-phosphate 3-epimerase and the UTP-glucose-1-phosphate uridylyltransferase genes.

“Therefore, metal depletion prompts an important remodeling of the metabolic flux in M genitalium,” the study authors wrote.

The investigators also looked into FUR-independent metal homeostasis, confirming genes that responded to metal starvation independent of FUR pathways.

Overall, the investigators uncovered a robust response to metal starvation. Understanding M genitalium’s response to nutrient deprivation will be helpful in developing new treatments for a pathogen which has demonstrated increasing antibiotic resistance in recent years.

“The regulation and metal transport systems identified in [M genitalium] represent very attractive therapeutic targets. This study will allow us to develop strategies to block metal acquisition through inhibitors or immunotherapy," said study author Òscar Quijada, PhD, professor of microbiology at Universitat Autónoma de Barcelona, in a press release.