Yersinia pestis

Ni-Glyoxalase I (GloI)#

Y. pestis possesses a confirmed nickel (Ni)-dependent Glyoxalase I that detoxifies methylglyoxal, the reactive and mutagenic byproduct of glycolysis.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓} During explosive growth in the host bloodstream (bacteremia can reach >10^8 CFU/mL in septicemic plague), high glycolytic flux generates toxic methylglyoxal concentrations.

Without nickel-GloI, the pathogen's own metabolism becomes self-poisoning—nickel availability is thus essential for sustained bacteremic growth. Human GloI uses Zinc, not nickel. This metal selectivity difference creates a potential target for selective inhibitors that would not affect host GloI.

Yersiniabactin (Ybt)#

Y. pestis produces yersiniabactin, the founding member of this siderophore/metallophore family.^{[2]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 2 ↓} Ybt binds iron(III) (Fe3+) with high affinity for classical iron acquisition during infection. Also chelates extracellular nickel and copper—a true multi-metal metallophore.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓}

The Ybt biosynthesis locus resides on the High Pathogenicity Island (HPI), which has been horizontally transferred to Klebsiella pneumoniae, UPEC Escherichia coli, and other Enterobacteriaceae—spreading multi-metal acquisition capability across pathogen families.

copper (Cu)-Ybt complexes may help Y. pestis resist copper toxicity encountered in macrophage phagosomes.

Other Iron Systems#

Yersiniabactin is the primary siderophore; Y. pestis also acquires heme via the Hmu system. Iron acquisition is tightly regulated by Fur (ferric uptake regulator).

Pathogenesis and Metal Context#

Flea transmission: Y. pestis forms a biofilm in the flea proventriculus, blocking blood feeding and forcing the flea to regurgitate bacteria during subsequent bites. Iron availability in the flea blood meal likely supports biofilm formation.

Bubonic plague: bacteria multiply in regional lymph nodes (buboes). Metal acquisition from lysed host cells provides iron and other metals. Septicemic plague: massive bloodstream infection.

The nickel (Ni)-GloI dependency is most critical during this phase due to the high metabolic rate.

Pneumonic plague: person-to-person airborne transmission. The most lethal form (near 100% mortality if untreated).

Clinical Significance#

Plague: untreated bubonic plague has 60-90% mortality; septicemic and pneumonic forms approach 100%. Approximately 1,000-2,000 cases reported annually to WHO, with foci in Africa, Asia, and the Americas. Bioterrorism: classified as a CDC Category A bioterrorism agent.

Aerosolized Y. pestis could cause pneumonic plague outbreaks.

Treatment requires rapid administration of aminoglycosides (streptomycin, gentamicin) or doxycycline. Multidrug-resistant strains have been documented in Madagascar.