Activity and interactions of antibiotic and phytochemical combinations against <i>Pseudomonas aeruginosa in vitro</i>

Jayaraman, Premkumar; Sakharkar, Meena Kishore; Lim, Chu Sing; Tang, Thean‐Hock; Sakharkar, Kishore R.

doi:10.7150/ijbs.6.556

Cited by 192 publications

(135 citation statements)

References 47 publications

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“…The antipseudomonas activity of BEB has been revealed to be rather weak (MIC≥512 µg/ml) (14,17). In accordance with this, the present study also found a relatively high MIC of BEB in P. aeruginosa.…”

Section: Discussionsupporting

confidence: 79%

“…The initial PA012 suspension (1x10 5 CFU/ml) was incubated with BEB and/or IMP at their concentrations at which synergism had been previously determined by using the checkerboard assay (17). The cells were counted at the designated time-points (0, 4, 8, 12 and 24 h).…”

Section: Time-kill (T-k) Testmentioning

confidence: 99%

“…Antagonism was defined as a decrease of ≥2log10 CFU/ml in the killing rate for the combined agents compared with the most active agent alone. Indifference was defined as a decrease of ≤2log10 CFU/ml in the killing rate for the combined agents compared with any of the two agents used alone (17).…”

Section: Time-kill (T-k) Testmentioning

confidence: 99%

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Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Fen

Wang

2017

Exp Ther Med

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Abstract. Pseudomonas (P.) aeruginosa is an ubiquitous and metabolically versatile opportunistic pathogen and may cause various life-threatening diseases. Due to increasing emergence of resistance to carbapenems, novel drugs with improved antibacterial activities compared with those of traditional antibiotics are required. In the present study, berberine (BEB), a natural isoquinoline alkaloid, was used in combination with imipenem (IMP), a commonly-used carbapenem, to investigate their antibacterial activities against a clinical P. aeruginosa isolate PA012 and the potential mechanism. Screening revealed that the minimum inhibitory concentrations (MICs) of BEB and IMP were 512 and 256 µg/ml, respectively. The combination of BEB (1/4 MIC) and IMP (1/8 MIC) exhibited a synergistic effect with a fractional inhibitory concentration index of 0.375. The synergism of BEB and IMP was also demonstrated in a time-kill test and by scanning electron microscopic observation. Treatment with BEB at ¼ MIC in combination with IMP at 1/16, 1/8, 1/4 and ½ MIC revealed a concentration-dependent promoting effect of IMP on the intracellular accumulation of BEB and inhibition of bacterial adhesion. Further analysis of gene expression revealed that BEB (1/4 MIC) combined with IMP (1/8 MIC) decreased MexZ, MexX, MexY and outer membrane protein (Opr)M by 38, 35, 46 and 49% in PA012. In conclusion, these results suggested that IMP had synergistic effects with BEB against the clinical isolate PA012 via inhibition of the MexXY-OprM efflux pump.

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Section: Discussionsupporting

confidence: 79%

Section: Time-kill (T-k) Testmentioning

confidence: 99%

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Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Fen

Wang

2017

Exp Ther Med

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“…22 We have previously shown that dietary phenolic compounds are effective against the intracellular bacterium C. pneumoniae. 17,18 As it has been proposed that natural compounds in combination with antibiotics could be a new strategy for developing therapies for infections caused by bacterial species and that natural plant products can potentiate the activity of antibiotics in combination, 23,24 we wanted to investigate whether coadministration of phenolic compounds with the antichlamydial compound doxycycline results in synergistic inhibition of acute C. pneumoniae infection. The combinations of natural phenols and doxycycline did not improve Interaction indices, inhibition percentage of C. pneumoniae growth in parenthesis, and host cell viability percentages in square brackets, are presented.…”

Section: Discussionmentioning

confidence: 99%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

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Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca 2+ ) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca 2+ modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca 2+ modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca 2+ modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 lM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 lM), whereas 10 lM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 lM and 100 lM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 lM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca 2+ modulators potentiate the antichlamydial effects of the phenolic compounds.

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“…Several studies have showed that phytochemicals can potentiate the activity of eradicating biofilm of antibiotics in combination (46)(47)(48)(49). The combinations of antibiotic sulfamethoxazole with protocatechuic acid/ellagic acid/gallic acid and tetracycline with gallic acid, cefoperazone with allicin showed synergistic mode of interaction and were highly effective in inhibition P. aeruginosa biofilm under in vitro conditions (50). Vitexin has been found to potentiate the anti-biofilm activity of azithromycin and gentamicin on P. aeruginosa (51).…”

Section: Discussionmentioning

confidence: 95%

Hyperoside inhibits biofilm formation of Pseudomonas aeruginosa

Sun

Feng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen in hospital-acquired infection and is readily able to form biofilms. Due to its high antibiotic resistance, traditional antibacterial treatments exert a limited effect on P. aeruginosa biofilm infections. It has been indicated that hyperoside inhibits P. aeruginosa PAO1 (PAO1) biofilm formation without affecting growth. Therefore, the current study examined the biofilm formation and quorum sensing (QS) system of PAO1 in the presence of hyperoside.Confocal laser scanning microscopy analysis demonstrated that hyperoside significantly inhibited biofilm formation. It was also observed that hyperoside inhibited twitching motility in addition to adhesion. Data from reverse transcription-quantitative polymerase chain reaction indicated that hyperoside inhibited the expression of lasR, lasI, rhlR and rhlI genes. These results suggest that the QS-inhibiting effect of hyperoside may lead to a reduction in biofilm formation. However, the precise mechanism of hyperoside on P. aeruginosa pathogenicity remains unclear and requires elucidation in additional studies. IntroductionPseudomonas aeruginosa (P. aeruginosa) is a common pathogen in hospital-acquired infections (1). Due to increasing multidrug resistance, P. aeruginosa infection is an increasingly common cause of mortality and morbidity (2). The mechanisms of antibiotic resistance in P. aeruginosa include the expression of multiple antibiotic modifying enzymes, antibiotic efflux pumps and acquisition of chromosomally or plasmid encoded antibiotic resistance genes. Additionally, chromosomal mutations and lower membrane permeability for the antibiotics also contribute to antibiotic resistance (3).P. aeruginosa is a biofilm-forming pathogen and is difficult to eradicate due to its high antibiotic resistance and the ability of the biofilm to evade the immune system (4-7). Quorum sensing (QS) is a system of stimuli and response correlated to population density. P. aeruginosa uses the QS system to coordinate gene expression according to the density of its local population. Thus, it can coordinate certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS inhibitors (QSIs) are the most well reported alternative therapeutics that can be used to overcome the problem of increasing antibiotic resistance in P. aeruginosa. QSIs target the virulence of the organism and therefore are also termed antipathogenic drugs. The virulence of P. aeruginosa depends on its cell-to-cell communication system, or QS system that uses diffusible signaling molecules that accumulate with increasing cell density and allows P. aeruginosa to trigger coordinated responses and achieve outcomes that would otherwise remain impossible to achieve by individual bacterium (8). Previous studies have demonstrated that traditional treatments for bacteria exert some effect on biofilm infections (9,10). Therefore, the effects of constituents from marine organisms, traditional Chinese herbs and plants (11-13) on biofilm infe...

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Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro

Cited by 192 publications

References 47 publications

Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

Hyperoside inhibits biofilm formation of Pseudomonas aeruginosa

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