BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

Aggarwal, Surya D.; Lees, John A.; Jacobs, Nathan T.; Bee, Gavyn Chern Wei; Abruzzo, Annie R.; Weiser, Jeffrey N.

doi:10.1016/j.chom.2022.10.015

Cited by 7 publications

(12 citation statements)

References 59 publications

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“…Previous studies report that microcin production is relevant in the host environment [68,69] where iron is often limiting. While microcins are not restricted to pathogenic strains, it has been proposed that pathogenic bacteria employ microcins to compete with other bacteria and promote their survival under the low iron conditions found in the host environment [41,51,70].…”

Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii ATCC 17978 encodes a microcin system with antimicrobial properties for contact-independent competition

et al. 2023

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Acinetobacter baumannii is a multidrug-resistant opportunistic pathogen that persists in the hospital environment and causes various clinical infections, primarily affecting immunocompromised patients. A. baumannii has evolved a wide range of mechanisms to compete with neighbouring bacteria. One such competition strategy depends on small secreted peptides called microcins, which exert antimicrobial effects in a contact-independent manner. Here, we report that A. baumannii ATCC 17978 (AB17978) encodes the class II microcin 17 978 (Mcc17978) with antimicrobial activity against closely related Acinetobacter , and surprisingly, also Escherichia coli strains. We identified the genetic locus encoding the Mcc17978 system in AB17978. Using classical bacterial genetic approaches, we determined that the molecular receptor of Mcc17978 in E. coli is the iron-catecholate transporter Fiu, and in Acinetobacter is Fiu’s homolog, PiuA. In bacteria, the Ferric uptake regulator (Fur) positively regulates siderophore systems and microcin systems under iron-deprived environments. We found that the Mcc17978 system is upregulated under low-iron conditions commonly found in the host environment and identified a putative Fur binding site upstream of the mcc17978 gene. When we tested the antimicrobial activity of Mcc17978 under different levels of iron availability, we observed that low iron levels not only triggered transcriptional induction of the microcin, but also led to enhanced microcin activity. Taken together, our findings suggest that A. baumannii may utilize microcins to compete with other microbes for resources during infection.

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Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii ATCC 17978 encodes a microcin system with antimicrobial properties for contact-independent competition

et al. 2023

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“…The chromosomally barcoded Spn 6A library was constructed as before [ 52 ]. Briefly, 7-nt barcodes of the sequence NNM CAATG NNM CAA N were obtained from a pE539 plasmid vector library.…”

Section: Methodsmentioning

confidence: 99%

“…The sequencing of barcoded Spn was performed as previously described [ 52 ]. Genomic DNA from samples was isolated using MasterPure Complete DNA & RNA Purification Kit (Lucigen, Middleton, WI) as per manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

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Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal disease

Lokken-Toyli,

Aggarwal,

Bee

et al. 2024

PLoS Pathog

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Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream. An increased rate of pneumococcal bacteremia in early life beyond the newborn period was attributed to increased bacterial translocation across the URT barrier. Bacterial dissemination in infant mice was independent of URT monocyte or neutrophil infiltration, phagocyte-derived ROS or RNS, inflammation mediated by toll-like receptor 2 or interleukin 1 receptor signaling, or the pore-forming toxin pneumolysin. Using molecular barcoding of Spn, we found that only a minority of bacterial clones in the nasopharynx disseminated to the blood in infant mice, indicating the absence of robust URT barrier breakdown. Rather, transcriptional profiling of the URT epithelium revealed a failure of infant mice to upregulate genes involved in the tight junction pathway. Expression of many such genes was also decreased in early life in humans. Infant mice also showed increased URT barrier permeability and delayed mucociliary clearance during the first two weeks of life, which corresponded with tighter attachment of bacteria to the respiratory epithelium. Together, these results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function facilitates bacterial dissemination.

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“…Thus, bacterial tissue burden can measure defects at the first and last bacteremia phases (initial site infection and avoiding immune clearance), but metrics to specifically quantify dissemination are lacking (10). Isogenic barcoding of bacteria has been used to study infection dynamics in various models (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). This approach enables the quantitative tracking of individual bacterial clones during different phases of infection, including the measurement of infection bottlenecks and clonal replication within tissues.…”

Section: Introductionmentioning

confidence: 99%

Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung

Holmes,

Dailey,

Hullahalli

et al. 2024

Preprint

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Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. Here, by barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we tracked pathogen dissemination following pneumonia. Variability in organ bacterial burdens was attributable to two distinct dissemination patterns distinguished by the extent of clonal expansion in the lungs. In metastatic dissemination, bacterial clones underwent heterogeneous clonal expansion within the lung and the dominant clones spread to secondary organs. In direct dissemination, bacterial clones exited the lungs without clonal expansion, leading to lower burdens in systemic sites. We uncover bacterial and host factors that govern these two modes of dissemination. Our data reveal unexpected heterogeneity in the dynamics of Klebsiella bacteremia and define a new paradigm for understanding within-host bacterial dissemination.

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BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

Cited by 7 publications

References 59 publications

Acinetobacter baumannii ATCC 17978 encodes a microcin system with antimicrobial properties for contact-independent competition

Acinetobacter baumannii ATCC 17978 encodes a microcin system with antimicrobial properties for contact-independent competition

Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal disease

Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung

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