Stealthy microbes: How Neisseria gonorrhoeae hijacks bulwarked iron during infection

Abstract

Transition metals are essential for metalloprotein function among all domains of life. Humans utilize nutritional immunity to limit bacterial infections, employing metalloproteins such as hemoglobin, transferrin, and lactoferrin across a variety of physiological niches to sequester iron from invading bacteria. Consequently, some bacteria have evolved mechanisms to pirate the sequestered metals and thrive in these metal-restricted environments. Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, causes devastating disease worldwide and is an example of a bacterium capable of circumventing human nutritional immunity. Via production of specific outer-membrane metallotransporters, N. gonorrhoeae is capable of extracting iron directly from human innate immunity metalloproteins. This review focuses on the function and expression of each metalloprotein at gonococcal infection sites, as well as what is known about how the gonococcus accesses bound iron.

Characterization of outer membrane vesicles released by clinical isolates of Neisseria gonorrhoeae

“…It is possible that regulatory and synthetic pathways that control OMV biogenesis were affected by genetic differences between the isolates. This may include iron uptake, known to be phase variable in N. gonorrhoeae [48]. Low iron levels control the expression of retrograde phospholipid shuttling channel MlaA resulting in hypervesiculating phenotype [22].…”

Transcriptome guided metabolic network analysis reveals rearrangements of carbon flux distribution inNeisseria gonorrhoeaeduring neutrophil co-culture

“…As a humanadapted pathogen, many of the molecular determinants driving the specificity for the human host are required for nutrient acquisition (4). Metabolic gene products involved in lactate acquisition, nutrient metal import, and anaerobiosis are all required for full Gc virulence in models of infection ranging from cell culture to murine genital colonization to experimental human urethral challenge (5)(6)(7)(8)(9)(10)(11)(12). However, many aspects of Gc metabolism remain undefined, such as the nutrients used by Gc in different infectious contexts and the core metabolic pathways required to sustain infection.…”