Zinc regulator and resistome identified in pathogenic bacteria

Researchers have discovered new ways bacteria respond to zinc – a metal used by the human immune system to destroy bacterial pathogens for destruction. Specifically, the researchers showed how a group of Streptococci used a copper regulator to control zinc poisoning, and they identified new genes involved in zinc resistance.

“This provides a new and fundamental understanding of how the pathogen carves a niche for itself in the human body,” said Kelvin Goh, PhD, a research associate at Griffith University in Queensland, Australia, and one of the study’s authors. was published in PLOS pathogens (“Regulatory crosstalk supports resistance to Zn intoxication in Streptococci“).

The work could pave the way for studies designing new strategies to treat bacterial infections without relying on antibiotics, which are quickly becoming obsolete because resistance continues to rise for them.

Streptococci are a large group of bacteria, some of which are ‘good’, such as those found in yogurt, and some of which are ‘bad’, such as causing nasty and sometimes deadly infections in humans. The researchers focused on group B Streptococci (GBS), which is usually harmless but can cause significant problems in the elderly or those with chronic conditions such as diabetes.

Metals such as zinc play an important role in the body’s ability to protect against bacterial infections. The researchers examined how GBS responds to zinc exposure and identified a number of ways in which the bacterium can withstand metal stress.

One of the ways the bacteria react to zinc is by using a regulator for a different metal copper (Cu).

“We saw how a genetic switch in [GBS] which usually detects and reacts to copper, also monitors the bacteria’s responses to zinc, discovering a nice mechanism of ‘crosstalk’ in the biological response to these two very different metals,” said Matthew Sullivan, PhD, senior research fellow at Griffith University and one of the authors of the study.

That “switch” is CopY. “RNAseq analysis of wild-type (WT) and to copy-deficient GBS subjected to metal stress revealed unique transcriptional connections between the Cu and Zn detoxification systems,” the authors wrote. “We show that CopY’s Cu-sensing role goes beyond Cu and enables CopY to regulate Cu and Zn stress responses that mediate changes in gene function for central cellular processes, including riboflavin synthesis. CopY also supported GBS intracellular survival in human macrophages and virulence during disseminated infection in mice.”

Goh added that the researchers also found “a series of unknown cellular processes that contribute to the survival of zinc and copper stress in bacteria.”

“Identification of the GBS Zn resistome using TraDIS revealed a set of genes essential for GBS growth under metal stress,” they wrote. “Several of the identified genes are novel to systems that support bacterial survival under metal stress and represent a diverse set of mechanisms that support microbial metal homeostasis during cell stress.”

“Overall, this study shows that copY controls discrete systems for Cu and Zn homeostasis in Streptococci and establishes a collection of new genomic elements that enable the bacteria to survive Zn intoxication,” they concluded.

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