In vivo growth of Staphylococcus lugdunensis is facilitated by the concerted function of heme and non-heme iron acquisition mechanisms

Flannagan, Ronald S.; Brozyna, Jeremy R; Kumar, Brijesh; Adolf, Lea Antje; Power, Jeffrey; Heilbronner, Simon; Heinrichs, David E.

doi:10.1016/j.jbc.2022.101823

Cited by 12 publications

(3 citation statements)

References 91 publications

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“…The latter is not recognized by EXFABP, thus allowing the S. Enteritidis to escape EXFABP-mediated growth inhibition under iron restriction (Julien et al, 2020). Additionally, Firmicutes is characterized by the acquisition of Fe 2+ via the FeoAB transport system and is independent of the siderophore (Polansky et al, 2015;Flannagan et al, 2022), which may be one of the causes that led to its increase after S. Enteritidis inoculation.…”

Section: Discussionmentioning

confidence: 99%

The response of cecal microbiota to inflammatory state induced by Salmonella enterica serovar Enteritidis

Liu

Miao

et al. 2022

Front. Microbiol.

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By combining the experiments of reciprocal crosses of chicken infected with Salmonella enterica serovar Enteritidis (S. Enteritidis), we focused on the common response of cecal microbiota to an inflammatory state in respect of transcriptome and microbiome. The inoculation of S. Enteritidis improved the microbial diversity and promoted the microbiota evolution in our infection model. Correlation analysis between bacteria and inflammation-related genes showed that some intestinal microorganisms were “inflammophile” and thrived in an inflamed environment. The global function of cecal microbiome was to maintain the homeostasis likely by the up-regulation of microbial metabolism pathway in bacitracin, putrescine, and flavonoids production, although the bacitracin may affect the symbiotic bacteria Enterococcus. The action of S. Enteritidis had close relationships with multiple inflammation-related genes, including the genes PTAFR, LY96, and ACOD1 which proteins are related to the binding and tolerance of LPS, and the genes IL-18, IL-18R1 and IL-18RAP which products can form a functional complex and transmit IL-18 pro-inflammatory signal. Additionally, the infection of S. Enteritidis aroused the transcription of EXFABP, which protein has a potential to sequestrate the siderophore and might cause the decline of Escherichia-Shigella and Enterococcus. S. Enteritidis can escape from the sequestrating through the salmochelin, another kind of siderophore which cannot be recognized by EXFABP. Probably by this way, S. Enteritidis competed with the symbiotic bacteria and edged out the niches. Our research can help to understand the interplay between host, pathogen, and symbiotic bacteria.

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Section: Discussionmentioning

confidence: 99%

The response of cecal microbiota to inflammatory state induced by Salmonella enterica serovar Enteritidis

Liu

Miao

et al. 2022

Front. Microbiol.

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“…It is worth considering that Isd-dependent heme acquisition in other pathogens appears to be is energized by specialized ATPases. This has been experimentally proven for S. lugdunensis where the ATPase IsdL (Heilbronner et al, 2011) energizes heme transport by IsdEF (Flannagan et al, 2022). Similarly, the isd loci of Bacillus anthracis (Skaar et al, 2006), Bacillus cereus (Abi-Khalil et al, 2015) and Listeria monocytogenes (Jin et al, 2006;Klebba et al, 2012) possess genes encoding putative ATPases.…”

Section: Discussionmentioning

confidence: 88%

Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition inStaphylococcus aureus

Adolf

Müller-Jochim

Kricks

et al. 2023

Preprint

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Sufficient access to transition metals such as iron is essential 24 for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains – FMMs) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.

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“…4) raising the question how it can interact with so many different bacteria in a mutualistic manner. S. lugdunensis has been found to be strongly impaired in growth on iron-deprived media [28], and experimental data indicated that S. lugdunensis is probably unable to synthesize iron-sequestering siderophores and may therefore depend on uptake of siderophores produced by other nasal bacteria [29, 30]. This possibility was assessed by monitoring the growth of S. lugdunensis on iron-deficient agar plates supplemented with culture filtrates from other nasal bacteria.…”

Section: Resultsmentioning

confidence: 99%

Siderophore piracy enables the nasal commensalStaphylococcus lugdunensisto antagonize the pathogenStaphylococcus aureus

Rosenstein,

Salazar,

Sauer

et al. 2024

Preprint

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Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes - beneficial "commensal" bacteria can often prevent the persistence of certain pathogens - using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and how S. lugdunensis carriage could be promoted to enhance its S. aureus-eliminating capacity. We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supporting commensals, and on the capacity of S. lugdunensis to import siderophores. These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

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In vivo growth of Staphylococcus lugdunensis is facilitated by the concerted function of heme and non-heme iron acquisition mechanisms

Cited by 12 publications

References 91 publications

The response of cecal microbiota to inflammatory state induced by Salmonella enterica serovar Enteritidis

The response of cecal microbiota to inflammatory state induced by Salmonella enterica serovar Enteritidis

Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition inStaphylococcus aureus

Siderophore piracy enables the nasal commensalStaphylococcus lugdunensisto antagonize the pathogenStaphylococcus aureus

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