Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Abstract

Uropathogenic Escherichia coli (UPEC) accounts for the majority of complicated and uncomplicated urinary tract infections. The use of phytomolecules in the treatment of UTI is fast gaining attention. The current report identifies a multidrug-resistant strain (QSLUPEC7), which is a strong biofilm producer, among the considered clinical isolates. The antimicrobial and antibiofilm activity was evaluated for the phytomolecule, Type A procyanidin (TAP) from Cinnamomum zeylanicum against QSLUPEC7. TAP treatment did not affect the growth of the MDR strain but affected the biofilm formation (∼70% inhibition). The confocal microscopic examination reveals the biofilm inhibition and the live cells in the biofilm corroborates the antimicrobial results. Further, the synergy studies of TAP and nitrofurantoin (NIT) were carried out at different pH. TAP acts synergistically with nitrofurantoin at different pH considered. A closer look in the results reveals that at pH 5.8, maximum growth inhibition is recorded. The gene expression analysis shows that TAP alone and in combination with NIT downregulates the major fimbriae adhesins of UPEC. The results conclude that the TAP has an antibiofilm activity against the multidrug-resistant strain of UPEC, without affecting the growth. Also, TAP reciprocally cooperates with nitrofurantoin at different pH by downregulating the adhesins of UPEC.

Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

“…A. hypogaea skin extracts display anti-microbial activity due to its A-type PAC content, able to prevent pathogen infection [ 36 ]. A-type PACs of Cinnamomum zeylanicum (Lauraceae family) were effective against uropathogenic E. coli multidrug-resistant strains and showed a marked antibiofilm activity [ 50 ]. Adhesion of Streptococcus pyogenes to human airway epithelial (HEp-2) cells was found to be inhibited by A-type PACs contained in Pelargonium sidoides (Geraniaceae family) extracts [ 97 ], whereas Pinus pinaster (Pinaceae family) bark extracts containing A-type PAC dimers showed bactericidal actions against Staphylococcus aureus and E. coli [ 102 ].…”

Cinnamomum: The New Therapeutic Agents for Inhibition of Bacterial and Fungal Biofilm-Associated Infection

“…Another study used Type A procyanidin (TAP) from C. zeylanicum to inhibit biofilm formation of MDR UPEC ( Vasudevan et al., 2020 ). Notably, procyanidin is one of Cinnamomum components with different biological activities.…”

“…Thus, by inhibiting bacterial adhesion, TAP may act as a suppressor of biofilm formation. In addition, the use of this substance may enhance the activity of antibiotics at low concentrations ( Vasudevan et al., 2020 ). As mentioned previously, Cinnamomum and its active components could be used to inhibit UPEC because, in addition to the appropriate antibacterial effect, it can also destroy bacterial biofilms.…”

Allicin suppressed Escherichia coli-induced urinary tract infections by a novel MALT1/NF-κB pathway

“…3,7,8 Nevertheless, a growing number of multidrug-resistant (MDR) E. coli mutant strains have been isolated in the past few years; these mutant strains have acquired more virulent bacterial factors and stronger pathogenicity. [9][10][11][12] The emergence of MDR bacteria has increased recurrence rates and unsatisfactory treatment efficacy, thereby threatening the quality of life of patients. 7,13 Therefore, exploring a novel hosttargeted therapy is appealing to combat MDR E. coli due to the low mutation rate of host genes compared with bacteria.…”

“…Recently, numerous plant-or food-derived antibacterial agents have been confirmed to be an effective remedy against UTIs caused by E. coli. 10,11,14 Garlic (Allium sativum L.), an aromatic herbaceous plant, has been used as food or a traditional remedy for centuries. 15,16 Garlic is rich in non-toxic polysulfides, including allicin, diallyl disulfide, and diallyl trisulfide among others.…”