The Bacterial Sec Pathway of Protein Export: Screening and Follow-Up

Crowther, Gregory J.; Weller, Sara M.; Jones, Jackson C.; Weaver, Tatiana; Fan, Erkang; Voorhis, Wesley C. Van; Rosen, Henry

doi:10.1177/1087057115587458

Cited by 8 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, the SecYEG channel located in the plasma membrane has been identified as a potential target for antibiotics against E. coli . Consequently, it was postulated that SecG may serve as the target for loratadine derivative Lo-7 in S.…”

Section: Resultsmentioning

confidence: 99%

“…20 Additionally, the SecYEG channel located in the plasma membrane has been identified as a potential target for antibiotics against E. coli. 21 Consequently, it was postulated that SecG may serve as the target for loratadine derivative Lo-7 in S. agalactiae. Utilizing molecular docking techniques, the potential binding affinity of SecG with the loratadine derivative Lo-7 was assessed.…”

Section: Potential Targeting Of Secg By the Loratadine Derivative Lo-...mentioning

confidence: 99%

See 1 more Smart Citation

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections

Cao,

Li,

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

The primary obstacles in the management of Enterococcus and Streptococcal infections are drug resistance and biofilm formation. Our study revealed that loratadine at a concentration of ≥25 μM exhibited significant inhibitory effects on biofilm formation in 167 clinical strains of Enterococcus faecalis and 15 clinical isolates of Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus pneumoniae. Additionally, the antibiofilm activity against E. faecalis and Streptococcal was demonstrated by several loratadine derivatives with altered side-chain carbamate moieties. This study investigated the antibacterial activity of the loratadine derivative Lo-7 against clinical strains of S. agalactiae and S. pyogenes, with minimum inhibitory concentrations ranging from 12.5 to 25 μM. The findings revealed that a low concentration of loratadine derivative Lo-7 (3.125 μM) significantly augmented the bactericidal efficacy of vancomycin against multidrug-resistant (MDR) S. agalactiae, both in vitro and in vivo. The loratadine derivative Lo-7, even at low concentrations, demonstrated significant efficacy in eliminating intracellular MDR S. agalactiae within macrophages, potentially indicating a unique advantage over vancomycin, linezolid, and loratadine. Mechanistically, exposure to the loratadine derivative Lo-7 resulted in membrane depolarization without affecting membrane permeability in S. agalactiae. The potential targeting of the SecG subunit of the SecYEG membrane-embedded channel by the loratadine derivative Lo-7 in S. agalactiae was identified through quantitative proteomics, a drug affinity responsive target stability assay, and molecular docking.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Potential Targeting Of Secg By the Loratadine Derivative Lo-...mentioning

confidence: 99%

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections

Cao,

Li,

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…NaN3 (sodium azide) is another inhibitor of SecA ATPase, which has been used in previous screens for inhibitors of the Sec-machinery as a positive control (9,(24)(25)(26). However, it is relatively non-selective, and can inhibit many other proteins as well (27).…”

Section: Assay Validation Using Compounds With Known Effectsmentioning

confidence: 99%

A whole cell luminescence-based screen for inhibitors of the bacterial Sec machinery

Salter,

Collinson,

Allen

2024

Preprint

View full text Add to dashboard Cite

There is a pressing need for new antibiotics to combat rising resistance to those already in use. The bacterial general secretion (Sec) system has long been considered a good target for novel antimicrobials thanks to its irreplacable role in maintaining cell envelope integrity; yet the lack of a robust, high-throughput method to screen for Sec inhibition has so far hampered efforts to realise this potential. Here, we have adapted our recently-developed in vitro assay for Sec activity - based on the split NanoLuc luciferase - to work at scale and in living cells. A simple counterscreen allows compounds that specifically target Sec to be distinguished from those with other effects on cellular function. As proof of principle we have applied this assay to a library of 5000 compounds and identified a handful of moderately effective in vivo inhibitors of Sec. We therefore anticipate that the methods presented here will be scalable to larger compound libraries, in the ultimate quest for Sec inhibitors with clinically relevant properties.

show abstract

Bacillus subtilis: current and future modification strategies as a protein secreting factory

Chen,

Li,

Yan

et al. 2024

World J Microbiol Biotechnol

View full text Add to dashboard Cite

The Bacterial Sec Pathway of Protein Export: Screening and Follow-Up

Cited by 8 publications

References 17 publications

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections

A whole cell luminescence-based screen for inhibitors of the bacterial Sec machinery

Bacillus subtilis: current and future modification strategies as a protein secreting factory

Contact Info

Product

Resources

About