Copper Efflux System Required in Murine Lung Infection by Haemophilus influenzae Composed of a Canonical ATPase Gene and Tandem Chaperone Gene Copies

Abstract

Copper is an essential micronutrient but is toxic at high concentrations. In Haemophilus influenzae mechanisms of copper resistance and its role in pathogenesis are unknown; however, our previous genetic screen by transposon insertion-site sequencing implicated a putative cation transporting ATPase ( copA ) in survival in a mouse lung infection model.

Moving metals: How microbes deliver metal cofactors to metalloproteins

“…Since the initial finding that E. hirae CopZ functions in resistance to excess Cu (Odermatt & Solioz, 1995), the role of CopZ‐like metallochaperones in bacterial metal homeostasis has been studied in several organisms (Checa et al, 2007; Crawford et al, 2020; Meydan et al, 2017; Solovieva & Entian, 2004). It appears that CopZ chaperones serve two primary conserved functions in Cu resistance: the delivery of Cu to P‐type ATPases for movement of the metal ions across biological membranes (Multhaup et al, 2001; Singleton & Le Brun, 2007; Utz et al, 2019), and the intracellular detoxification of excess Cu ions, likely through sequestration (Corbett et al, 2011; Rivera‐Millot et al, 2021; Wong et al, 2023). However, CopZ proteins have also been shown to transfer Cu to bacterial Cu‐responsive transcriptional regulators that serve in mounting the adaptive response to elevated Cu concentrations (Cobine et al, 1999; Novoa‐Aponte et al, 2019).…”