Influence of Short Cationic Lipopeptides with Fatty Acids of Different Chain Lengths on Bacterial Biofilms Formed on Polystyrene and Hydrogel Surfaces

Nowadays, biomaterials are applied in many different branches of medicine. They significantly improve the patients’ comfort and quality of life, but also constitute a significant risk factor for biofilm-associated infections. Currently, intensive research on the development of novel materials resistant to microbial colonization as well as new compounds that are active against biofilms is being carried out. Within this research, antimicrobial peptides (AMPs) and their analogues are being intensively investigated due to their promising antimicrobial activities. The main goal of this study was to synthesize and evaluate the antimicrobial efficacy of short cationic lipopeptides that were designed to imitate the features of AMPs responsible for antimicrobial activities: positive net charge and amphipacity. The positive charge of the molecules results from the presence of basic amino acid residues: arginine and lysine. Amphipacity is provided by the introduction of decanoic, dodecanoic, tetradecanoic, and hexadecanoic acid chains to the molecules. Lipopeptides (C16-KR-NH2, C16-KKK-NH2, C16-KKC-NH2, C16-KGK-NH2, C14-KR-NH2, C14-KKC-NH2, C12-KR-NH2, C12-KKC-NH2, and (C10)2-KKKK-NH2) were synthesized using a novel solid-phase temperature-assisted methodology. The minimum inhibitory concentrations (MICs), minimum biofilm eradication concentrations (MBECs), and minimum biofilm formation inhibitory concentrations (MBFICs) were determined for the following bacterial strains: Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 14990, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, and Proteus mirabilis PCM 543. The biofilms were cultured on two types of surfaces: polystyrene plates (PS) and contact lenses (CL). The lipopeptides exhibited the ability to inhibit the growth of bacteria in a liquid medium as well as on the PS and CL. The compounds also eliminated the bacterial biofilm from the surface of both materials. In general, the activity against gram-positive bacteria was stronger in comparison to that against gram-negative strains. There were certain discrepancies between the activity of compounds against the biofilm cultured on PS and CL. This was especially noticeable for staphylococci—the lipopeptides presented much higher activity against biofilm formed on the PS surface. It is worth noting that the obtained MBEC values for lipopeptides were usually only a few times higher than the MICs. The results of the performed experiments suggest that further studies on lipopeptides and their potential application in the treatment and prophylaxis of biofilm-associated infections should be conducted.

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Bandage contact lens and topical steroids are risk factors for the development of microbial keratitis after epithelium-off CXL

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2018-000231 ◽

2019 ◽

Vol 4 (1) ◽

pp. e000231 ◽

Cited By ~ 4

Author(s):

Argyrios Tzamalis ◽

Vito Romano ◽

Robert Cheeseman ◽

Riccardo Vinciguerra ◽

Mark Batterbury ◽

...

Keyword(s):

Risk Factors ◽

Contact Lenses ◽

Significant Risk ◽

Significant Risk Factor ◽

Topical Steroids ◽

Microbial Keratitis ◽

Corneal Haze ◽

Group 2 ◽

Topical Antimicrobial ◽

Group 1

ObjectiveTo investigate the role of bandage contact lenses (BCL) and topical steroids as risk factors for the development of microbial keratitis after epithelium-off corneal collagen cross-linking (CXL).Methods and AnalysisPatients undergoing CXL between February 2011 and July 2017 were included. Patients were divided into two groups: those who were treated postoperatively with a BCL, topical antimicrobial and steroids (group 1) and those who received only a topical antimicrobial until healing of the epithelial defect before introduction of topical steroids (group 2).Results1273 eyes of 964 patients were included. Group 1 comprised 316 eyes and group 2 comprised 957 eyes. There were no significant differences in the presence of persisting corneal haze or scarring between the two groups (p=0.57). Microbial keratitis occurred in nine eyes (0.71% of eyes) of eight (0.83%) patients (one case was bilateral) out of 1273 eyes. Staphylococcus aureus was cultured from corneal scrapes in seven out of nine (77.8%) cases and from contiguous sites in the two cases. All cases occurred in group 1 (incidence=2.85%) and none in group 2 (p<0.0001). A greater proportion of patients who developed microbial keratitis were atopic (75%, p=0.4).ConclusionThe use of BCL and topical steroids prior to healing of the epithelium is a significant risk factor for microbial keratitis. S. aureus is the most common micro-organism and is likely to originate from an endogenous site. Not using a BCL and delaying the introduction of topical steroids until epithelial healing significantly reduce the risk of developing microbial keratitis without increasing the risk of persistent corneal haze.

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Effect of polymer type on the colonization of plastic pellets by marine bacteria

FEMS Microbiology Letters ◽

10.1093/femsle/fnab026 ◽

2021 ◽

Vol 368 (5) ◽

Author(s):

Josefine Hansen ◽

Jette Melchiorsen ◽

Nicole Ciacotich ◽

Lone Gram ◽

Eva C Sonnenschein

Keyword(s):

Bacterial Colonization ◽

Amplicon Sequencing ◽

Bacterial Biofilm ◽

Microbial Colonization ◽

Natural Seawater ◽

Bacterial Strains ◽

Initial Inoculum ◽

Plastic Type ◽

Polymer Type ◽

Hydrocarbon Degraders

Abstract Plastic is omnipresent in the oceans and serves as a surface for biofilm-forming microorganisms. Plastic debris comprises different polymers, which may influence microbial colonization; here, we evaluated whether polymer type affects bacterial biofilm formation. Quantifying the biofilm on polyethylene (PE), polypropylene (PP) or polystyrene (PS) pellets by six marine bacterial strains (Vibrio,Pseudoalteromonas,Phaeobacter) demonstrated that each strain had a unique colonization behavior with either a preference for PS or PP over the other polymer types or no preference for a specific plastic type. PE, PP and PS pellets were exposed to natural seawater microbiota using free-living or total communities as inoculum. Microbial assembly as determined by 16S rRNA (V4) amplicon sequencing was affected by the composition of the initial inoculum and also by the plastic type. Known polymer and hydrocarbon degraders such as Paraglaciecola, Oleibacter and Hydrogenophaga were found in the plastic biofilms. Thus, on a community level, bacterial colonization on plastic is influenced by the microorganisms as well as the polymer type, and also individual strains can demonstrate polymer-specific colonization.

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Ultrashort Cationic Lipopeptides–Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis

Molecules ◽

10.3390/molecules25020257 ◽

2020 ◽

Vol 25 (2) ◽

pp. 257 ◽

Cited By ~ 5

Author(s):

Damian Neubauer ◽

Maciej Jaśkiewicz ◽

Marta Bauer ◽

Krzysztof Gołacki ◽

Wojciech Kamysz

Keyword(s):

Fatty Acid ◽

Amino Acid ◽

Antimicrobial Agents ◽

Basic Amino Acid ◽

Amino Acid Residues ◽

Bacterial Strains ◽

Fatty Acid Chain ◽

N Terminus ◽

Arginine Residues ◽

The Impact

Ultrashort cationic lipopeptides (USCLs) are promising antimicrobial agents that hypothetically may be alternatively used to combat pathogens such as bacteria and fungi. In general, USCLs consist of fatty acid chains and a few basic amino acid residues. The main shortcoming of USCLs is their relatively high cytotoxicity and hemolytic activity. This study focuses on the impact of the hydrophobic fatty acid chain, on both antimicrobial and hemolytic activities. To learn more about this region, a series of USCLs with different straight-chain fatty acids (C8, C10, C12, C14) attached to the tripeptide with two arginine residues were synthesized. The amino acid at the N-terminal position was exchanged for proteinogenic and non-proteinogenic amino acid residues (24 in total). Moreover, the branched fatty acid residues were conjugated to N-terminus of a dipeptide with two arginine residues. All USCLs had C-terminal amides. USCLs were tested against reference bacterial strains (including ESKAPE group) and Candida albicans. The hemolytic potential was tested on human erythrocytes. Hydrophobicity of the compounds was evaluated by RP-HPLC. Shortening of the fatty acid chain and simultaneous addition of amino acid residue at N-terminus were expected to result in more selective and active compounds than those of the reference lipopeptides with similar lipophilicity. Hypothetically, this approach would also be beneficial to other antimicrobial peptides where N-lipidation strategy was used to improve their biological characteristics.

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Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽

10.1027/0227-5910/a000271 ◽

2014 ◽

Vol 35 (5) ◽

pp. 330-337 ◽

Cited By ~ 14

Author(s):

Cun-Xian Jia ◽

Lin-Lin Wang ◽

Ai-Qiang Xu ◽

Ai-Ying Dai ◽

Ping Qin

Keyword(s):

Risk Factor ◽

Family Income ◽

Rural China ◽

Significant Risk ◽

Significant Risk Factor ◽

Health Condition ◽

Physical Illness ◽

Rural Residents ◽

Increased Risk ◽

Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

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Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19872317 ◽

1987 ◽

Vol 52 (9) ◽

pp. 2317-2325 ◽

Cited By ~ 5

Author(s):

Jan Hlaváček ◽

Jan Pospíšek ◽

Jiřina Slaninová ◽

Walter Y. Chan ◽

Victor J. Hruby

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

The Other ◽

Amino Acid Residues ◽

Phase Synthesis ◽

Other Hand ◽

Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

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Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19941439 ◽

1994 ◽

Vol 59 (6) ◽

pp. 1439-1450 ◽

Cited By ~ 2

Author(s):

Miroslava Žertová ◽

Jiřina Slaninová ◽

Zdenko Procházka

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Basic Amino Acid ◽

The Other ◽

Side Chain ◽

Inhibitory Potency ◽

Phase Synthesis ◽

Other Hand ◽

Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

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Primary- and secondary-structural analysis of a unique prokaryotic metallothionein from a Synechococcus sp. cyanobacterium

Biochemical Journal ◽

10.1042/bj2510691 ◽

1988 ◽

Vol 251 (3) ◽

pp. 691-699 ◽

Cited By ~ 106

Author(s):

R W Olafson ◽

W D McCubbin ◽

C M Kay

Keyword(s):

Amino Acid ◽

Metal Binding ◽

Helical Structure ◽

Basic Amino Acid ◽

Cysteine Residues ◽

Amino Acid Residues ◽

C Terminus ◽

Empirical Relations ◽

Heavy Metal Binding ◽

Synechococcus Sp

Biochemical and physiological studies of Synechococcus cyanobacteria have indicated the presence of a low-Mr heavy-metal-binding protein with marked similarity to eukaryotic metallothioneins (MTs). We report here the characterization of a Synechococcus prokaryotic MT isolated by gel-permeation and reverse-phase chromatography. The large number of variants of this molecule found during chromatographic separation could not be attributed to the presence of major isoproteins as assessed by amino acid analysis and amino acid sequencing of isoforms. Two of the latter were shown to have identical primary structures that differed substantially from the well-described eukaryotic MTs. In addition to six long-chain aliphatic residues, two aromatic residues were found adjacent to one another near the centre of the molecule, making this the most hydrophobic MT to be described. Other unusual features included a pair of histidine residues located in repeating Gly-His-Thr-Gly sequences near the C-terminus and a complete lack of association of hydroxylated residues with cysteine residues, as is commonly found in eukaryotes. Similarly, aside from a single lysine residue, no basic amino acid residues were found adjacent to cysteine residues in the sequence. Most importantly, sequence alignment analyses with mammalian, invertebrate and fungal MT sequences showed no statistically significant homology aside from the presence of Cys-Xaa-Cys structures common to all MTs. On the other hand, like other MTs, the prokaryotic molecule appears to be free of alpha-helical structure but has a considerable amount of beta-structure, as predicted by both c.d. measurements and the Chou & Fasman empirical relations. Considered together, these data suggested that some similarity between the metal-thiolate clusters of the prokaryote and eukaryote MTs may exist.

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Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers

BMC Gastroenterology ◽

10.1186/s12876-020-01580-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Junya Arai ◽

Jun Kato ◽

Nobuo Toda ◽

Ken Kurokawa ◽

Chikako Shibata ◽

...

Keyword(s):

Risk Factors ◽

Activities Of Daily Living ◽

Daily Living ◽

Poor Prognosis ◽

Significant Risk ◽

Care Facility ◽

Significant Risk Factor ◽

Advanced Age ◽

Gastroduodenal Ulcers ◽

Poor Outcomes

Abstract Background Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. Methods In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. Results Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08–16.2), and heart disease (OR 3.05; 95% CI 1.11–8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36–28.7). Conclusion In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

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Neurodevelopmental outcome of healthy term newborn with serum bilirubin >15 mg/dl at one year

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-200511 ◽

2020 ◽

pp. 1-6

Author(s):

P. Dubey ◽

J. Shrivastava ◽

B.P. Choubey ◽

A. Agrawal ◽

V. Thakur

Keyword(s):

Serum Bilirubin ◽

Tertiary Care ◽

Neurodevelopmental Outcome ◽

Significant Risk ◽

Central India ◽

Significant Risk Factor ◽

Motor Domain ◽

Medical Emergency ◽

One Year ◽

Group 1

BACKGROUND: Neonatal hyperbilirubinemia is a common medical emergency in early neonatal period. Unconjugated bilirubin is neurotoxic and can lead to lifelong neurological sequelae in survivors. OBJECTIVE: To find out the association between serum bilirubin and neurodevelopmental outcome at 1 year of age using Development Assessment Scale for Indian Infants (DASII). METHODS: A prospective cohort study was conducted in the Department of Pediatrics of a tertiary care institution of Central India between January 2018 and August 2019. Total 108 term healthy neonates, with at least one serum bilirubin value of >15 mg/dl, were included. Subjects were divided into three groups based on the serum bilirubin; group 1: (15–20 mg/dl) –85(78.7%) cases, group 2: (20–25 mg/dl) –17(15.7%), and group 3: (>25 mg/dl) –6(5.5%). Developmental assessment was done using DASII at 3, 6, 9, 12 months of age. RESULTS: Out of 108 cases, 101(93.5%) received phototherapy, and 7(6.5%) received double volume exchange transfusion. Severe delay was observed in 5(4.6%) and mild delay in 2(1.9%) cases in the motor domain of DASII at one year. Severe delay in the motor domain was associated with mean TSB of 27.940±2.89 mg/dl and mild delay with mean TSB of 22.75±1.76 mg/dl (p = 0.001). On cluster analysis, delay was observed in locomotion 1 score in 11(13%) cases (p = 0.003) and manipulation score in 6(7.1%) cases in group 1. CONCLUSION: Increased serum bilirubin was a significant risk factor for the delayed neurodevelopment in babies with neonatal jaundice. Even a moderate level of bilirubin significantly affects the developmental outcome.

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