Staphylococcus aureus lacking a functional MntABC manganese import system has increased resistance to copper

Abstract

Staphylococcus aureus continues to be a serious public health concern as S. aureus infections result in high morbidity and mortality rates (Turner et al., 2019). Although historically known as a nosocomial pathogen, there has been an increase in community-acquired (CA) S. aureus cases among both immunocompetent and immunocompromised groups (Tenover et al., 2006). These CA S. aureus strains often cause skin and soft tissue infections that can develop into invasive and systemic infections (Turner et al., 2019). Treatment of S. aureus infections is complicated due to the ability of this pathogen to evolve and/or acquire resistance to antibiotics (Malachowa and DeLeo, 2010). To combat these problems, we need to develop new prevention and therapeutic approaches including the characterization of new promising antimicrobial targets.Copper (Cu) is gaining popularity as an antimicrobial but killing or preventing the growth of microorganisms using Cu is an age-old technology (Dollwet and Sorenson, 1985;Grass et al., 2011). Copper is increasingly used as an intrinsic antibacterial and in metallic copper or copper-containing alloys on touch surfaces (Grass et al., 2011). Mammals also use Cu to help clear infections by increasing Cu loads at sites of inflammation (Beveridge et al., 1985;Hodgkinson and Petris, 2012). Cu accumulates within macrophage intracellular vesicles (Achard et al., 2012) and ultimately in phagosomes (Wagner et al., 2005). The addition of Cu to macrophages increases killing efficiency and genetic depletion of the Cu

Cetylpyridinium Trichlorostannate: Synthesis, Antimicrobial Properties, and Controlled-Release Properties via Electrical Resistance Tomography

“…A Staphylococcus aureus Los Angeles County clone (LAC) is a community-acquired methicillin-resistant S. aureus (MRSA) strain and a representative of the USA300 epidemic strain in the USA. 65 Salmonella enterica serovar Typhimurium is a leading cause of salmonellosis worldwide. 66 Streptococcus mutans is a leading cause of dental caries.…”

Regulation of Bacterial Manganese Homeostasis and Usage During Stress Responses and Pathogenesis

“…Some evidence exists that excess Mn can interfere with copper (Cu) homeostasis and vice versa (Johnson et al, 2015;Martin et al, 2017b). In UPEC, Cu import was shown to confer Mndependent protection against ROS, while in S. aureus Cu import caused mismetallation of Mn-enzymes with Cu (Saenkham et al, 2020;Al-Tameemi et al, 2021). In UPEC, sublethal doses of Cu increased MnSOD levels which helped UPEC survive in macrophages (Saenkham et al, 2020).…”

“…In UPEC, sublethal doses of Cu increased MnSOD levels which helped UPEC survive in macrophages (Saenkham et al, 2020). In the S. aureus study, which mimicked infection conditions in the mammalian host, a low Mn:high Cu ratio caused MntABC to inappropriately import sufficient Cu to cause toxicity, via mismetallation of NrdEF and the Fe-S dehydratase AcnA (Al-Tameemi et al, 2021).…”

Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus

“…Noteworthy, RsaC could also interconnect and balance various metallostasis systems (Fe and Zn) ( Lalaouna et al, 2019 ), but is apparently not involved in the MntABC-mediated increased resistance to copper ( Al-Tameemi et al, 2021 ).…”