Targeting bacterial transferrin and lactoferrin receptors for vaccines

Schryvers, Anthony B.

doi:10.1016/j.tim.2022.01.017

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…Lactoferrin-based nanocarrier formulations are promising options to deliver drugs to hard-to-treat intracellular bacteria and even more challenging cases such as biofilms. , Their small size, ability to encapsulate both hydrophobic and hydrophilic drugs, and potential for targeted drug delivery are credited to this. Lactoferrin receptors are expressed on many cells including lung epithelial cells, macrophages, brain endothelial cells, liver cells, and cancer cells as well as some pathogenic bacteria, making them suitable to target therapeutic agents to these cells through receptor-mediated endocytosis. − S. aureus for instance has been shown to deploy receptors such as GAPDH, iron-regulated surface determinant protein (IsdA), and lactoferrin binding protein B (LbpB) among others − ,− to extract iron from lactoferrin and other host iron-carrying proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Lactoferrin receptors are expressed on many cells including lung epithelial cells, macrophages, brain endothelial cells, liver cells, and cancer cells as well as some pathogenic bacteria, making them suitable to target therapeutic agents to these cells through receptor-mediated endocytosis. 52 − 54 S. aureus for instance has been shown to deploy receptors such as GAPDH, iron-regulated surface determinant protein (IsdA), and lactoferrin binding protein B (LbpB) among others 9 − 12 , 55 − 57 to extract iron from lactoferrin and other host iron-carrying proteins. While there is scanty information about M. abscessus iron acquisition, mycobacteria in general have evolved mechanisms for iron acquisition, and lactoferrin is a potential source of iron for these bacteria.…”

Section: Discussionmentioning

confidence: 99%

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Targeting Intracellular Bacteria with Dual Drug-loaded Lactoferrin Nanoparticles

Andima,

Boese,

Paul

et al. 2024

ACS Infect. Dis.

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Treatment of microbial infections is becoming daunting because of widespread antimicrobial resistance. The treatment challenge is further exacerbated by the fact that certain infectious bacteria invade and localize within host cells, protecting the bacteria from antimicrobial treatments and the host's immune response. To survive in the intracellular niche, such bacteria deploy surface receptors similar to host cell receptors to sequester iron, an essential nutrient for their virulence, from host iron-binding proteins, in particular lactoferrin and transferrin. In this context, we aimed to target lactoferrin receptors expressed by macrophages and bacteria; as such, we prepared and characterized lactoferrin nanoparticles (Lf-NPs) loaded with a dual drug combination of antimicrobial natural alkaloids, berberine or sanguinarine, with vancomycin or imipenem. We observed increased uptake of drug-loaded Lf-NPs by differentiated THP-1 cells with up to 90% proportion of fluorescent cells, which decreased to about 60% in the presence of free lactoferrin, demonstrating the targeting ability of Lf-NPs. The encapsulated antibiotic drug cocktail efficiently cleared intracellular Staphylococcus aureus (Newman strain) compared to the free drug combinations. However, the encapsulated drugs and the free drugs alike exhibited a bacteriostatic effect against the hard-to-treat Mycobacterium abscessus (smooth variant). In conclusion, the results of this study demonstrate the potential of lactoferrin nanoparticles for the targeted delivery of antibiotic drug cocktails for the treatment of intracellular bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting Intracellular Bacteria with Dual Drug-loaded Lactoferrin Nanoparticles

Andima,

Boese,

Paul

et al. 2024

ACS Infect. Dis.

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“…Due to its function, and the amino acid composition of its iron-binding site, it is the requirement for a synergistic anion to ensure tight iron-binding [43]. After ferric iron ion passed though TbpA pores, it bounds with a second iron binding protein FbpA [40].…”

Section: Discussionmentioning

confidence: 99%

Molecular Detection and Genotyping of P. Multocida, M. Hemolytica, and B. Trehalosi Isolates Targeting the Virulence Associated Genes from Ethiopian Cattle and Sheep

2022

JGEBR

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Pasteurellaceae families are usually considered opportunistic pathogens which inhabit normal flora on the mucosal membranes of the upper respiratory and the lower genital tracts of mammals and birds. The majority of P. multocida, M. hemolytica, and B. trehalosi isolates are opportunistic animal pathogens and cause disease only under certain conditions. Some of the target genes are shared by isolates found in the same or different genera.. The alpha / beta hydrolase kmt1 genes part of OMP and SLP are shared by all P.multocida species and FbpA is common gene for both P.multocida and M. hemolytica isolates. Other virulence related genes are used for genotyping of P.multocida, M.hemolytica and B.trehalosi isolates. The objective of the current research was focused on the detection and genotyping of different target genes that can be found in the isolates of P. multocida, M. hemolytica, and B. trehalosi using various PCR primers. The distributions of virulence-associated genes were assessed in the isolates of the three genera. Materials and methods A total of eight isolates from P. multocida, M. hemolytica, and B. trehalosi isolated from clinical cases of cattle and sheep and stored at the Bacteriology laboratory of NVI were used as source of samples for the present study. DNeasy® Blood & Tissue Kit (Qiagen, Germany) was used for the extraction of DNA from bacterial isolates. Different primers were used for genotyping of P. multocida, P.hemolytica and B.trehalosi isolates. Results P.multocida was detected using species-specific kmt1 primer with an amplicon product of 460bp. Four serogroups of P.multocida (A, B, D, &E) were detected using serotype-specific primers with amplification products of 1044bp, 760bp, 657bp, and 511bp respectively. PCR was conducted to HS causing P.multocida type B and detected 620 bp amplicons. SLP genes were detected in all P.multocida serotypes with an amplification product size 1400-1553bp. In addition to that, the four P. multocida serotypes were found to be positive for BRD-PmSLP with an amplification product of 460bp but using recombinant HS-SLP primers resulted in the double band at 460 bp and 541bp for serotypes A and D. However, HS causing type B& E serotypes were detected with an amplified product of 541bp. TbpA2 has been detected with an amplicon size of approximately 750 bp for types (A and D) and 1300bp for type B using TbpA-F2/Rev primers. All of the P.multocida serotypes (A, B, D&E) and M. hemolytica (A: 1) were strongly positive for the iron acquisition FbpA gene with amplification bands at 500bp and 1000bp, respectively. A multiplex PCR as-say was carried out for detection of M. haemolytica A: 1 using PHSSA and Rpt2 primers with amplification products of 327pb and 1022 bp respectively. The three isolates of B. trehalosi were identified using BtsodA primers with the result of 144bp amplicon size. Conclusion From this work, we understood that P.multocida and M. haemolytica shared genetic materials like iron binding proteins (FbpA) and some of the target genes (kmt1 and SLP) were commonly found in all isolates of P. multocida. However, TbpA2 was found to be in most but not in all Pasteurella isolates. We also observed that PHSSA and Rpt2 genes were exclusively found in M. hemolytica isolates whereas Bt-sodA was prominent in all B. trehalosi isolates (T3, T4&T15).

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“…Because of the importance of metal acquisition to N . gonorrhoeae colonization and infection, its metal acquisition systems are potential targets for vaccines and therapeutics to combat the rise in antibiotic-resistant gonorrhea [ 1 ]. Here, we review the nutritional immunity challenges faced by N .…”

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confidence: 99%

“…N. gonorrhoeae has unique ways to subvert nutritional immunity, particularly by producing transporters that bind and extract metals from human metal-sequestering proteins. Because of the importance of metal acquisition to N. gonorrhoeae colonization and infection, its metal acquisition systems are potential targets for vaccines and therapeutics to combat the rise in antibiotic-resistant gonorrhea [1]. Here, we review the nutritional immunity challenges faced by N. gonorrhoeae with a particular focus on iron and zinc, how N. gonorrhoeae overcomes nutritional immunity for successful infection, and open questions for future investigation.…”

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confidence: 99%