Pseudomonas aeruginosa zinc uptake in chelating environment is primarily mediated by the metallophore pseudopaline

ABSTRACT Airway infections associated with cystic fibrosis (CF) are polymicrobial. We reported previously that clinical isolates of Pseudomonas aeruginosa promote the growth of a variety of streptococcal species. To explore the mechanistic basis of this interaction, we performed a genetic screen to identify mutants of Streptococcus sanginuis SK36 whose growth was no longer enhanced by P. aeruginosa PAO1. Mutations in the zinc uptake systems of S. sanguinis SK36 reduced growth of these strains by 1 to 3 logs compared to that of wild-type S. sanguinis SK36 when grown in coculture with P. aeruginosa PAO1, and exogenous zinc (0.1 to 10 μM) rescued the coculture defect of zinc uptake mutants of S. sanguinis SK36. Zinc uptake mutants of S. sanguinis SK36 had no obvious growth defect in monoculture. Consistent with competition for zinc driving coculture dynamics, S. sanguinis SK36 grown in coculture with P. aeruginosa showed increased expression of zinc uptake genes compared to that of S. sanguinis grown alone. Strains of P. aeruginosa PAO1 defective in zinc transport also supported ∼2-fold more growth by S. sanguinis compared to that in coculture with wild-type P. aeruginosa PAO1. An analysis of 118 CF sputum samples revealed that total zinc levels varied from ∼5 to 145 μM. At relatively low zinc levels, Pseudomonas and Streptococcus spp. were found in approximately equal abundance; at higher zinc levels, we observed a decline in relative abundance of Streptococcus spp., perhaps as a result of increasing zinc toxicity. Together, our data indicate that the relative abundances of these microbes in the CF airway may be impacted by zinc levels. IMPORTANCE Polymicrobial infections in CF cases likely impact patient health, but the mechanism(s) underlying such interactions is poorly understood. Here, we show using an in vitro model system that interactions between Pseudomonas and Streptococcus are modulated by zinc availability, and clinical data are consistent with this model. Together with previous studies, our work supports a role for metal homeostasis as a key factor driving microbial interactions.

Download Full-text

Efficient zinc uptake is critical for the ability of Pseudomonas aeruginosa to express virulence traits and colonize the human lung

Journal of Trace Elements in Medicine and Biology ◽

10.1016/j.jtemb.2018.03.009 ◽

2018 ◽

Vol 48 ◽

pp. 74-80 ◽

Cited By ~ 4

Author(s):

Maria Chiara Mastropasqua ◽

Iain Lamont ◽

Lois W. Martin ◽

David W. Reid ◽

Melania D’Orazio ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Human Lung ◽

Zinc Uptake ◽

Virulence Traits

Download Full-text

The Transcriptional Regulator Np20 Is the Zinc Uptake Regulator in Pseudomonas aeruginosa

PLoS ONE ◽

10.1371/journal.pone.0075389 ◽

2013 ◽

Vol 8 (9) ◽

pp. e75389 ◽

Cited By ~ 28

Author(s):

Matthew L. Ellison ◽

John Matthew Farrow ◽

Whitney Parrish ◽

Allison S. Danell ◽

Everett C. Pesci

Keyword(s):

Pseudomonas Aeruginosa ◽

Transcriptional Regulator ◽

Zinc Uptake ◽

Zinc Uptake Regulator

Download Full-text

The zinc uptake system (znuA Locus) is important for bacterial adhesion and virulence in Pseudomonas Aeruginosa

Biomedical Engineering and Environmental Engineering ◽

10.1201/b18419-30 ◽

2015 ◽

pp. 135-142

Author(s):

Bo Li ◽

Bobo Wang ◽

Xiangli Gao ◽

Lang Gao ◽

Ying Liang ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Bacterial Adhesion ◽

Zinc Uptake ◽

Uptake System

Download Full-text

Strategies for Zinc Uptake in Pseudomonas aeruginosa at the Host–Pathogen Interface

Frontiers in Microbiology ◽

10.3389/fmicb.2021.741873 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuaitao Wang ◽

Juanli Cheng ◽

Yanting Niu ◽

Panxin Li ◽

Xiangqian Zhang ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Drug Targets ◽

Storage Proteins ◽

S100 Protein ◽

Zinc Uptake ◽

Pathogenic Microorganisms ◽

The Face ◽

Host Defense System ◽

Zinc Levels ◽

Zinc Uptake Regulator

As a structural, catalytic, and signaling component, zinc is necessary for the growth and development of plants, animals, and microorganisms. Zinc is also essential for the growth of pathogenic microorganisms and is involved in their metabolism as well as the regulation of various virulence factors. Additionally, zinc is necessary for infection and colonization of pathogenic microorganisms in the host. Upon infection in healthy organisms, the host sequesters zinc both intracellularly and extracellularly to enhance the immune response and prevent the proliferation and infection of the pathogen. Intracellularly, the host manipulates zinc levels through Zrt/Irt-like protein (ZIP)/ZnT family proteins and various zinc storage proteins. Extracellularly, members of the S100 protein family, such as calgranulin C, sequester zinc to inhibit microbial growth. In the face of these nutritional limitations, bacteria rely on an efficient zinc transport system to maintain zinc supplementation for proliferation and disruption of the host defense system to establish infection. Here, we summarize the strategies for zinc uptake in conditional pathogenic Pseudomonas aeruginosa, including known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and the zinc uptake regulator (Zur). In addition, other potential zinc uptake pathways were analyzed. This review systematically summarizes the process of zinc uptake by P. aeruginosa to provide guidance for the development of new drug targets.

Download Full-text