scholarly journals Effects of colistin and tigecycline on multidrug-resistant Acinetobacter baumannii biofilms: advantages and disadvantages of their combination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshinori Sato ◽  
Tsuneyuki Ubagai ◽  
Shigeru Tansho-Nagakawa ◽  
Yusuke Yoshino ◽  
Yasuo Ono

AbstractWe investigated the antimicrobial effects of colistin (CST) and tigecycline (TGC), either alone or in combination, on biofilm-dispersed and biofilm-embedded multidrug-resistant Acinetobacter baumannii (MDRAB) strains R1 and R2. The bacterial growth of biofilm-dispersed MDRAB was inhibited by CST or TGC. However, the inhibitory effects were attenuated by a combination of CST and low concentrations of TGC. The bactericidal effects of CST, but not TGC, were observed on biofilm-dispersed MDRAB. Notably, the bactericidal effects increased with a combination of CST and high concentrations of TGC, whereas they were attenuated with the combination of CST and low concentrations of TGC. Although biofilm formation by MDRAB decreased with increasing concentrations of CST or TGC, there was no complete disruption of the biofilms. Additionally, the biofilms increased with a combination of 1–2 μg/mL CST and TGC at 2 μg/mL and 2–4 μg/mL for strains R1 and R2, respectively. Biofilm-embedded MDRAB was eradicated with CST, but not TGC. Notably, the eradication effects increased with a combination of CST and high concentrations of TGC, whereas attenuation happened with the combination of CST and low concentrations of TGC. These results provide information on the combined effects of CST and TGC in the treatment of biofilm-associated MDRAB infection.

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Gregory A. Knauf ◽  
Ashley L. Cunningham ◽  
Misha I. Kazi ◽  
Ian M. Riddington ◽  
Alexander A. Crofts ◽  
...  

ABSTRACTQuaternary amine compounds (QAC) are potent antimicrobials used to prevent the spread of pathogenic bacteria. While they are known for their membrane-damaging properties, QAC action has been suggested to extend beyond the surface to intracellular targets. Here we characterize the range of action of the QAC biocide benzalkonium chloride (BZK) against the bacterial pathogenAcinetobacter baumannii. At high concentrations, BZK acts through membrane disruption, but at low concentrations we show that wide-spread protein aggregation is associated with BZK-induced cell death. Resistance to BZK is found to develop through ribosomal protein mutations that protectA. baumanniiagainst BZK-induced protein aggregation. The multifunctional impact of BZK led us to discover that alternative QAC structures, with low human toxicity, retain potent action against multidrug-resistantA. baumannii,Staphylococcus aureus, andClostridium difficileand present opportunities for their development as antibiotics.IMPORTANCEQuaternary amine compounds (QACs) are widely used to prevent the spread of bacterial pathogens, but our understanding of their mode of action is incomplete. Here we describe disruption of bacterial proteostasis as an unrecognized action of QAC antimicrobial action and uncover the potential of diverse QAC structures to act as multitarget antibiotics.


Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1186 ◽  
Author(s):  
Chaitany Jayprakash Raorane ◽  
Jin-Hyung Lee ◽  
Jintae Lee

Multi-drug resistant Acinetobacter baumannii is well-known for its rapid acclimatization in hospital environments. The ability of the bacterium to endure desiccation and starvation on dry surfaces for up to a month results in outbreaks of health care-associated infections. Previously, indole and its derivatives were shown to inhibit other persistent bacteria. We found that among 16 halogenated indoles, 5-iodoindole swiftly inhibited A. baumannii growth, constrained biofilm formation and motility, and killed the bacterium as effectively as commercial antibiotics such as ciprofloxacin, colistin, and gentamicin. 5-Iodoindole treatment was found to induce reactive oxygen species, resulting in loss of plasma membrane integrity and cell shrinkage. In addition, 5-iodoindole rapidly killed three Escherichia coli strains, Staphylococcus aureus, and the fungus Candida albicans, but did not inhibit the growth of Pseudomonas aeruginosa. This study indicates the mechanism responsible for the activities of 5-iodoindole warrants additional study to further characterize its bactericidal effects on antibiotic-resistant A. baumannii and other microbes.


2021 ◽  
Vol 22 (11) ◽  
pp. 5540
Author(s):  
Min Ji Hong ◽  
Min Kyung Kim ◽  
Yoonkyung Park

An amphipathic α-helical peptide, Hp1404, was isolated from the venomous gland of the scorpion Heterometrus petersii. Hp1404 exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus but is cytotoxic. In this study, we designed antimicrobial peptides by substituting amino acids at the 14 C-terminal residues of Hp1404 to reduce toxicity and improve antibacterial activity. The analog peptides, which had an amphipathic α-helical structure, were active against gram-positive and gram-negative bacteria, particularly multidrug-resistant Acinetobacter baumannii, and showed lower cytotoxicity than Hp1404. N-phenyl-1-naphthylamine uptake and DisC3-5 assays demonstrated that the peptides kill bacteria by effectively permeating the outer and cytoplasmic membranes. Additionally, the analog peptides inhibited biofilm formation largely than Hp1404 at low concentrations. These results suggest that the analog peptides of Hp1404 can be used as therapeutic agents against A. baumannii infection.


1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.


2007 ◽  
Vol 56 (12) ◽  
pp. 1595-1599 ◽  
Author(s):  
Justin Edwards ◽  
Geeta Patel ◽  
David W. Wareham

Acinetobacter baumannii is increasingly recognized as an important multidrug-resistant nosocomial pathogen. Recent work has highlighted enhanced growth and heightened virulence in the presence of ethyl alcohols. As alcohol-based hand rubs (ABHRs) are extensively used in health care settings, the authors set out to determine whether the hand rubs could also influence the growth of prevalent multidrug-resistant strains circulating in UK hospitals. A significant increase in growth was observed when minimal media were supplemented with concentrations of 1 % and lower of four commercially available hand rubs. In addition, growth in ABHR-supplemented media resulted in secretion of proteins into the culture supernatant. One of these was identified as OmpA, which is recognized as having emulsifying activity, which could potentially confer enhanced pathogenicity to A. baumannii.


2021 ◽  
Vol 53 (1) ◽  
pp. 111-126
Author(s):  
Y. F. Huang ◽  
E. H. Zhang ◽  
X. H. Zhang ◽  
Q. Wang ◽  
H. Z. Wang ◽  
...  

We investigated the autotoxicity of Lanzhou lily rhizosphere soil with different cultivation years. The allelochemicals in such soils were isolated and identified by gas chromatography-mass spectrometry (GC-MS). Based on our earlier studies, the antioxidant 2246 and dioctyl terephthalate were found in lily sick soil were used in pot experiments determine to their autotoxic effects on the Lanzhou lily seedlings growth, photosynthetic parameters and antioxidant enzyme activities in seedling leaves. The content of antioxidant 2246 and dioctyl terephthalate was determined by GC-MS in rhizosphere soil of different cultivation years. The aqueous extracts of Lanzhou lily rhizosphere soil promoted the growth of its own seedlings at 0.2 mg·mL-1, however, the concentrations > 2 mg·mL-1 were inhibitory. The longer the cultivation period (1-yr, 2-yr and 4-yr), the stronger were the inhibitory effects. In rhizosphere soils of 1-yr, 2-yr and 4-yr ; 8,: 15 and 18 compounds were identified, respectively. The identified compounds were camphor, 3-hydroxy-4-methoxy-benzaldehyde, 2,4-bis(1,1- dimethylethyl)-phenol, tributyl phosphate, dibutyl phthalate, antioxidant 2246 and dioctyl terephthalater and these are reported as allelochemicals. The pot experiment results showed that low concentrations of antioxidant 2246 stimulated the seedling growth but high concentrations were inhibitory, while all concentrations of dioctyl terephthalater inhibited the seedling growth. At 100 mg·mL-1, the antioxidant 2246 and dioctyl terephthalate significantly inhibited the photosynthesis and antioxidant enzyme activity in leaves (P <0.05). Furthermore, the content of these two compounds in soils increased with the increase of cultivation years. These results suggested that allelochemicals accumulated in replanted soil contributed to the autotoxicity of Lanzhou lily in rhizosphere soil.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhonghui Pu ◽  
Huaqiao Tang ◽  
Nana Long ◽  
Min Qiu ◽  
Mingxiang Gao ◽  
...  

Abstract Background Multidrug-resistant pathogens are resistant to many antibiotics and associated with serious infections. Amomum tsaoko Crevost et Lemaire, Sanguisorba officinalis, Terminalia chebula Retz and Salvia miltiorrhiza Bge, are all used in Traditional Chinese Medicine (TCM) against multidrug-resistant pathogens, and the purpose of this study was to evaluate the antibacterial and anti-virulence activity of extracts derived from them. Methods The antibacterial activity of ethanol and aqueous extracts from these four plants was examined against several multi-drug resistant bacterial strains, and their anti-virulence potential (including quorum quenching activity, biofilm inhibition, and blocking production of virulence factor δ-toxin) was assessed against different S. aureus strains. The chemical composition of the most effective extract was determined by LC-FTMS. Results Only extracts from S. officinalis and A. tsaoko were shown to exhibit limited growth inhibition activity at a dose of 256 μg·mL-1. The S. officinalis ethanol extract, the ethanol and aqueous extract of A. tsaoko, and the aqueous extract of S. miltiorrhiza all demonstrated quorum quenching activity, but didn’t significantly inhibit bacterial growth. The ethanol extract of S. officinalis inhibited bacterial toxin production and biofilm formation at low concentrations. Chemical composition analysis of the most effective extract of S. officinalis showed that it mainly contained saponins. Conclusions The most active extract tested in this study was the ethanol root extract of S. officinalis. It inhibited δ-toxin production and biofilm formation at low concentrations and saponins may be its key active components. While the four plants showed no direct antibacterial effects, their anti-virulence properties may be key to fighting bacterial infections.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Udomluk Leungtongkam ◽  
Rapee Thummeepak ◽  
Thawatchai Kitti ◽  
Kannipa Tasanapak ◽  
Jintana Wongwigkarn ◽  
...  

Abstract In this study, we examined the association between antimicrobial resistance, CRISPR/Cas systems and virulence with phage susceptibility in Acinetobacter baumannii and investigated draft genomes of phage susceptible multidrug resistant A. baumannii strains from Thailand. We investigated 230 A. baumannii strains using 17 lytic A. baumannii phages and the phage susceptibility was 46.5% (107/230). Phage susceptibility was also associated with resistance to numerous antibiotics (p-value < 0.05). We also found association between biofilm formation and the presence of ompA gene among phage susceptible A. baumannii strains (p-value < 0.05). A. baumannii isolates carrying cas5 or combinations of two or three other cas genes, showed a significant increase in phage resistance. Whole-genome sequences of seven phage susceptible A. baumannii isolates revealed that six groups of antibiotic resistance genes were carried by all seven phage susceptible A. baumannii. All strains carried biofilm associated genes and two strains harbored complete prophages, acquired copper tolerance genes, and CRISPR-associated (cas) genes. In conclusion, our data exhibits an association between virulence determinants and biofilm formation among phage susceptible A. baumannii strains. These data help to understand the bacterial co-evolution with phages.


Biofouling ◽  
2020 ◽  
Vol 36 (4) ◽  
pp. 492-504 ◽  
Author(s):  
Saima Muzammil ◽  
Mohsin Khurshid ◽  
Iqra Nawaz ◽  
Muhammad Hussnain Siddique ◽  
Muhammad Zubair ◽  
...  

Author(s):  
María-Guadalupe Avila-Novoa ◽  
Oscar-Alberto Solís-Velázquez ◽  
Daniel-Eduardo Rangel-López ◽  
Jean-Pierre González-Gómez ◽  
Pedro-Javier Guerrero-Medina ◽  
...  

Acinetobacter baumannii is an important opportunistic pathogen that shows resistance to cephalosporins, penicillins, carbapenems, fluoroquinolones, and aminoglycosides, the multiresistance being associated with its ability to form biofilms in clinical environments. The aim of this study was to determine biofilm formation and its potential association with genes involved in antibiotic resistance mechanisms of A. baumannii isolates of different clinical specimens. We demonstrated 100% of the A. baumannii isolates examined to be multidrug resistant (MDR), presenting a 73.3% susceptibility to cefepime and a 53.3% susceptibility to ciprofloxacin. All A. baumannii isolates were positive for blaOXA-51, 33.3% being positive for blaOXA-23 and ISAba1, and 73.3% being positive for gyrA. We found 86.6% of A. baumannii strains to be low-grade biofilm formers and 13.3% to be biofilm negative; culturing on Congo red agar (CRA) plates revealed that 73.3% of the A. baumannii isolates to be biofilm producers, while 26.6% were not. These properties, combined with the role of A. baumannii as a nosocomial pathogen, increase the probability of A. baumannii causing nosocomial infections and outbreaks as a complication during therapeutic treatments and emphasize the need to control A. baumannii biofilms in hospital environments.


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