AI Article Synopsis
- Group A Streptococcus (GAS) is a serious human pathogen that relies on zinc for growth but can be harmed by excessive zinc levels.
- The host's immune response uses nutritional strategies to limit zinc availability or increase zinc toxicity, impacting GAS survival and infection.
- GAS has developed adaptive mechanisms, including specialized metal transporters, to counteract these host defenses, highlighting the potential for new treatments that target GAS's metal acquisition systems.
Article Abstract
Group A Streptococccus (GAS) is a major human pathogen that causes significant morbidity and mortality. Zinc is an essential trace element required for GAS growth, however, zinc can be toxic at excess concentrations. The bacterial strategies to maintain zinc sufficiency without incurring zinc toxicity play a crucial role in host-GAS interactions and have a significant impact on GAS pathogenesis. The host deploys nutritional immune mechanisms to retard GAS growth by causing either zinc deprivation or zinc poisoning. However, GAS overcomes the zinc-dependent host defenses and survives in the hostile environment by employing complex adaptive strategies. In this review, we describe the different host immune strategies that employ either zinc limitation or zinc toxicity in different host environments to control GAS infection. We also discuss the molecular mechanisms and machineries used by GAS to evade host nutritional defenses and establish successful infection. Emerging evidence suggests that the metal transporters are major GAS virulence factors as they compete against host nutritional immune mechanisms to acquire or expel metals and promote bacterial survival in the host. Thus, identification of GAS molecules and elucidation of the mechanisms by which GAS combats host-mediated alterations in zinc availability may lead to novel interference strategies targeting GAS metal acquisition systems.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730477 | PMC |
| http://dx.doi.org/10.1039/c7mt00240h | DOI Listing |
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