scholarly journals The multi-faceted mechano-bactericidal mechanism of nanostructured surfaces

2020 ◽  
Vol 117 (23) ◽  
pp. 12598-12605 ◽  
Author(s):  
Elena P. Ivanova ◽  
Denver P. Linklater ◽  
Marco Werner ◽  
Vladimir A. Baulin ◽  
XiuMei Xu ◽  
...  
Keyword(s):  
Cell Death ◽  
Bactericidal Activity ◽  
Mechanical Energy ◽  
Bactericidal Effect ◽  
Bacterial Cells ◽  
Gram Stain ◽  
Nanostructured Surfaces ◽  
Bacterial Cell Death ◽  
Antibacterial Surfaces ◽  
Nanopillar Arrays

The mechano-bactericidal activity of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, particularly in the current era of emerging antibiotic resistance. This work demonstrates the effects of an incremental increase of nanopillar height on nanostructure-induced bacterial cell death. We propose that the mechanical lysis of bacterial cells can be influenced by the degree of elasticity and clustering of highly ordered silicon nanopillar arrays. Herein, silicon nanopillar arrays with diameter 35 nm, periodicity 90 nm and increasing heights of 220, 360, and 420 nm were fabricated using deep UV immersion lithography. Nanoarrays of 360-nm-height pillars exhibited the highest degree of bactericidal activity toward both Gram stain-negativePseudomonas aeruginosaand Gram stain-positiveStaphylococcus aureusbacteria, inducing 95 ± 5% and 83 ± 12% cell death, respectively. At heights of 360 nm, increased nanopillar elasticity contributes to the onset of pillar deformation in response to bacterial adhesion to the surface. Theoretical analyses of pillar elasticity confirm that deflection, deformation force, and mechanical energies are more significant for the substrata possessing more flexible pillars. Increased storage and release of mechanical energy may explain the enhanced bactericidal action of these nanopillar arrays toward bacterial cells contacting the surface; however, with further increase of nanopillar height (420 nm), the forces (and tensions) can be partially compensated by irreversible interpillar adhesion that reduces their bactericidal effect. These findings can be used to inform the design of next-generation mechano-responsive surfaces with tuneable bactericidal characteristics for antimicrobial surface technologies.

scholarly journals Model-Driven Controlled Alteration of Nanopillar Cap Architecture Reveals its Effects on Bactericidal Activity

2020 ◽  
Vol 8 (2) ◽  
pp. 186 ◽  
Author(s):  
Taiyeb Zahir ◽  
Jiri Pesek ◽  
Sabine Franke ◽  
Jasper Van Pee ◽  
Ashish Rathore ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Cell Envelope ◽  
Antibacterial Properties ◽  
Biophysical Model ◽  
Surface Measurement ◽  
Dependent Manner ◽  
Bending Rigidity ◽  
Nanostructured Surfaces ◽  
Model Driven ◽  
Antibacterial Surfaces

Nanostructured surfaces can be engineered to kill bacteria in a contact-dependent manner. The study of bacterial interactions with a nanoscale topology is thus crucial to developing antibacterial surfaces. Here, a systematic study of the effects of nanoscale topology on bactericidal activity is presented. We describe the antibacterial properties of highly ordered and uniformly arrayed cotton swab-shaped (or mushroom-shaped) nanopillars. These nanostructured surfaces show bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa. A biophysical model of the cell envelope in contact with the surface, developed ab initio from the infinitesimal strain theory, suggests that bacterial adhesion and subsequent lysis are highly influenced by the bending rigidity of the cell envelope and the surface topography formed by the nanopillars. We used the biophysical model to analyse the influence of the nanopillar cap geometry on the bactericidal activity and made several geometrical alterations of the nanostructured surface. Measurement of the bactericidal activities of these surfaces confirms model predictions, highlights the non-trivial role of cell envelope bending rigidity, and sheds light on the effects of nanopillar cap architecture on the interactions with the bacterial envelope. More importantly, our results show that the surface nanotopology can be rationally designed to enhance the bactericidal efficiency.

scholarly journals Antibiotic Bactericidal Activity Is Countered by Maintaining pH Homeostasis in Mycobacterium smegmatis

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
I. L. Bartek ◽  
M. J. Reichlen ◽  
R. W. Honaker ◽  
R. L. Leistikow ◽  
E. T. Clambey ◽  
...  
Keyword(s):  
Cell Death ◽  
Bactericidal Activity ◽  
Mycobacterium Smegmatis ◽  
Drug Target ◽  
Multidrug Resistant ◽  
Proton Pumping ◽  
Drug Resistant ◽  
Bacterial Cells ◽  
Ph Homeostasis ◽  
Content Type

ABSTRACT Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our findings suggest a mechanism of antibiotic killing that stems from the antibiotic’s ability to increase the pH within bacterial cells by disrupting proton entry without affecting proton pumping out of cells. Knowledge of the core mechanism necessary for antibiotic killing could have a significant impact on the development of new lethal antibiotics and for the treatment of recalcitrant and drug-resistant pathogens. Antibiotics target specific biosynthetic processes essential for bacterial growth. It is intriguing that several commonalities connect the bactericidal activity of seemingly disparate antibiotics, such as the numerous conditions that confer broad-spectrum antibiotic tolerance. Whether antibiotics kill in a manner unique to their specific targets or by a universal mechanism is a critical and contested subject. Herein, we demonstrate that the bactericidal activity of diverse antibiotics against Mycobacterium smegmatis and four evolutionarily divergent bacterial pathogens was blocked by conditions that worked to maintain intracellular pH homeostasis. Single-cell pH analysis demonstrated that antibiotics increased the cytosolic pH of M. smegmatis, while conditions that promoted proton entry into the cytosol prevented intracellular alkalization and antibiotic killing. These findings led to a hypothesis that posits antibiotic lethality occurs when antibiotics obstruct ATP-consuming biosynthetic processes while metabolically driven proton efflux is sustained despite the loss of proton influx via ATP synthase. Consequently, without a concomitant reduction in respiratory proton efflux, cell death occurs due to intracellular alkalization. Our findings indicate the effects of antibiotics on pH homeostasis should be considered a potential mechanism contributing to antibiotic lethality. IMPORTANCE Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our findings suggest a mechanism of antibiotic killing that stems from the antibiotic’s ability to increase the pH within bacterial cells by disrupting proton entry without affecting proton pumping out of cells. Knowledge of the core mechanism necessary for antibiotic killing could have a significant impact on the development of new lethal antibiotics and for the treatment of recalcitrant and drug-resistant pathogens.

scholarly journals Mechano-bactericidal mechanism of graphene nanomaterials

2018 ◽  
Vol 8 (3) ◽  
pp. 20170060 ◽  
Author(s):  
Denver P. Linklater ◽  
Vladimir A. Baulin ◽  
Saulius Juodkazis ◽  
Elena P. Ivanova
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Pore Formation ◽  
Lipid Extraction ◽  
Bactericidal Effect ◽  
Mechanical Contact ◽  
Physical Damage ◽  
Cell Inactivation ◽  
Bacterial Cell Death ◽  
Bactericidal Effects

Growing interest in the bactericidal effect of graphene and graphene-derived nanomaterials has led to the investigation and effective publication of the bactericidal effects of the substratum, many of which present highly conflicting material. The nature of bacterial cell death on graphene bio-interfaces, therefore, remains poorly understood. Here, we review recent findings on the bactericidal effect of graphene and graphene-derived nanomaterials, and proposed mechanisms of cell inactivation, due to mechanical contact with graphene materials, including lipid extraction, physical damage to membranes and pore formation.

scholarly journals Фототермическое действие инфракрасного (808 nm) лазерного излучения и наночастиц золота в различных модификациях на S. aureus

2020 ◽  
Vol 128 (6) ◽  
pp. 840
Author(s):  
Е.С. Тучина ◽  
В.В. Тучин
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Laser Radiation ◽  
Power Density ◽  
Suspended Matter ◽  
Bacterial Population ◽  
Bacterial Cells ◽  
Glass Substrates ◽  
Bacterial Cell Death ◽  
Pronounced Inhibition

The effect of infrared laser radiation (808 nm) of different fluence rates on the bacteria Staphylococcus aureus 209 P, incubated in solutions of gold nanocubes, nanorods and on glass substrates with fixed nanodiscs, was studied. Radiation with a power density of 60 mW/cm2 in combination with nanocubes caused the death of 50% of the bacterial population after 30 min of exposure, in combination with nanostructures - 56%. An increase in the temperature of suspended matter after irradiation was found of no more than 5-6 °C. Radiation with a power density of 400 mW/cm2 caused a pronounced inhibition of the viability of bacterial cells – by 81% after 30 min. Incubation of microorganism suspensions on the surface of glass substrate containing gold nanodiscs during irradiation (808 nm, 400 mW/cm2) resulted in 99% of bacterial cell death.

scholarly journals Iron-dependent essential genes in Salmonella Typhimurium

2017 ◽  
Author(s):  
Sardar Karash ◽  
Young Min Kwon
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Essential Gene ◽  
Iron Concentration ◽  
Essential Genes ◽  
Mutagenic Action ◽  
Bacterial Cells ◽  
Antibiotic Development ◽  
Bacterial Cell Death

AbstractBackgroundThe molecular mechanisms underlying bacterial cell death due to stresses or bactericidal antibiotics are complex and remain puzzling. Previously, it was shown that iron is required for effective killing of bacterial cells by numerous bactericidal antibiotics. Here, our high-resolution Tn-seq analysis demonstrated that transposon mutants of S. Typhimurium with insertions in essential genes escaped immediate killing or growth inhibition under iron-restricted conditions for approximately one-third of all essential genes.ResultsWe grouped essential genes into two categories, iron-dependent and iron-independent essential genes. The iron-dependency of the iron-dependent essential genes was further validated by the fact that the relative abundance of these essential gene mutants increased further with more severe iron restrictions. Our unexpected observation can be explained well by the recently proposed common killing mechanisms of bactericidal antibiotics via production of reactive oxygen species (ROS). In this model iron restriction would inhibit production of ROS, leading to reduced killing activity following blocking of an essential function. Interestingly, the targets of most antibiotics currently in use clinically, whether bacteriostatic or bactericidal, are iron-dependent essential genes.ConclusionsOur result suggests that targeting iron-independent essential genes may be a better strategy for future antibiotic development, because blocking these genes would lead to immediate cell death regardless of iron concentration. On the contrary, blocking iron-dependent pathways under iron limited in vivo environment could lead to reduced killing action, which might increase drug-resistance by mutagenic action of sublethal concentrations of ROS. This work expands our knowledge on the role of iron to a broader range of essential pathways, and provides novel insights for development of more effective antibiotics.

scholarly journals A Fish Galectin-8 Possesses Direct Bactericidal Activity

2020 ◽  
Vol 22 (1) ◽  
pp. 376
Author(s):  
Tengfei Zhang ◽  
Shuai Jiang ◽  
Li Sun
Keyword(s):  
Bactericidal Activity ◽  
Bacterial Pathogens ◽  
Bactericidal Effect ◽  
Immune Defense ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Animal Cells ◽  
Gram Negative ◽  
Tongue Sole ◽  
Wide Range

Galectins are a family of animal lectins with high affinity for β-galactosides. Galectins are able to bind to bacteria, and a few mammalian galectins are known to kill the bound bacteria. In fish, no galectins with direct bactericidal effect have been reported. In the present study, we identified and characterized a tandem repeat galectin-8 from tongue sole Cynoglossus semilaevis (designated CsGal-8). CsGal-8 possesses conserved carbohydrate recognition domains (CRDs), as well as the conserved HXNPR and WGXEE motifs that are critical for carbohydrate binding. CsGal-8 was constitutively expressed in nine tissues of tongue sole and up-regulated in kidney, spleen, and blood by bacterial challenge. When expressed in HeLa cells, CsGal-8 protein was detected both in the cytoplasm and in the micro-vesicles secreted from the cells. Recombinant CsGal-8 (rCsGal-8) bound to lactose and other carbohydrates in a dose dependent manner. rCsGal-8 bound to a wide range of gram-positive and gram-negative bacteria and was co-localized with the bound bacteria in animal cells. Lactose, fructose, galactose, and trehalose effectively blocked the interactions between rCsGal-8 and different bacteria. Furthermore, rCsGal-8 exerted potent bactericidal activity against some gram-negative bacterial pathogens by directly damaging the membrane and structure of the pathogens. Taken together, these results indicate that CsGal-8 likely plays an important role in the immune defense against some bacterial pathogens by direct bacterial interaction and killing.

scholarly journals Hyperbaric Oxygen Sensitizes Anoxic Pseudomonas aeruginosa Biofilm to Ciprofloxacin

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Mette Kolpen ◽  
Christian J. Lerche ◽  
Kasper N. Kragh ◽  
Thomas Sams ◽  
Klaus Koren ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hyperbaric Oxygen ◽  
Bactericidal Activity ◽  
Host Response ◽  
Polymorphonuclear Leukocytes ◽  
Bactericidal Effect ◽  
Aerobic Respiration ◽  
Hyperbaric Oxygen Treatment ◽  
Content Type ◽  
Oxygen Treatment

ABSTRACT Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm, which is subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility of biofilms remain unclear, but accumulating evidence suggests that the efficacy of several bactericidal antibiotics is enhanced by stimulation of aerobic respiration of pathogens, while lack of O2 increases their tolerance. In fact, the bactericidal effect of several antibiotics depends on active aerobic metabolism activity and the endogenous formation of reactive O2 radicals (ROS). In this study, we aimed to apply hyperbaric oxygen treatment (HBOT) to sensitize anoxic P. aeruginosa agarose biofilms established to mimic situations with intense O2 consumption by the host response in the cystic fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress, and increased bacterial growth. The findings highlight that oxygenation by HBOT improves the bactericidal activity of ciprofloxacin on P. aeruginosa biofilm and suggest that bacterial biofilms are sensitized to antibiotics by supplying hyperbaric O2.

scholarly journals N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Xin Li ◽  
Jane Kim ◽  
Jiabin Wu ◽  
Alaa’ I Ahamed ◽  
Yinsheng Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Diabetic Mouse ◽  
Bacterial Survival ◽  
Bacterial Cell Death ◽  
Carboxylic Groups ◽  
Acetyl Cysteine

Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α-tocopherol, N-acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS). We hypothesize that NAC creates a microenvironment that affects bacterial survival and EPS integrity. To test this hypothesis, we developed an in vitro biofilm system using microbiome taken directly from diabetic mouse chronic wounds. For these studies, we chose mice in which chronic wound microbiome was rich in Pseudomonas aeruginosa (97%). We show that NAC at concentrations with pH < pKa causes bacterial cell death and breakdown of EPS. When used before biofilm is formed, NAC leads to bacterial cell death whereas treatment after the biofilm is established NAC causes biofilm dismantling accompanied by bacterial cell death. Mechanistically, we show that NAC can penetrate the bacterial membrane, increase oxidative stress, and halt protein synthesis. We also show that low pH is important for the actions of NAC and that bacterial death occurs independently of the presence of biofilm. In addition, we show that both the acetyl and carboxylic groups play key roles in NAC functions. The results presented here provide insight into the mechanisms by which NAC dismantles biofilm and how it could be used to treat chronic wounds after debridement (NAC applied at the start of culture) or without debridement (NAC applied when biofilm is already formed). This approach can be taken to develop biofilm from microbiome taken directly from human chronic wounds to test molecules that could be effective for the treatment of specific biofilm compositions.

scholarly journals Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest

2020 ◽  
Vol 117 (8) ◽  
pp. 4358-4367 ◽  
Author(s):  
David W. Basta ◽  
David Angeles-Albores ◽  
Melanie A. Spero ◽  
John A. Ciemniecki ◽  
Dianne K. Newman
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Death ◽  
Heat Shock ◽  
Protein Aggregation ◽  
Protein Quality ◽  
Growth Arrest ◽  
Cellular Level ◽  
Secondary Response ◽  
Bacterial Cells ◽  
Encoding Genes

When nutrients in their environment are exhausted, bacterial cells become arrested for growth. During these periods, a primary challenge is maintaining cellular integrity with a reduced capacity for renewal or repair. Here, we show that the heat-shock protease FtsH is generally required for growth arrest survival of Pseudomonas aeruginosa, and that this requirement is independent of a role in regulating lipopolysaccharide synthesis, as has been suggested for Escherichia coli. We find that ftsH interacts with diverse genes during growth and overlaps functionally with the other heat-shock protease-encoding genes hslVU, lon, and clpXP to promote survival during growth arrest. Systematic deletion of the heat-shock protease-encoding genes reveals that the proteases function hierarchically during growth arrest, with FtsH and ClpXP having primary, nonredundant roles, and HslVU and Lon deploying a secondary response to aging stress. This hierarchy is partially conserved during growth at high temperature and alkaline pH, suggesting that heat, pH, and growth arrest effectively impose a similar type of proteostatic stress at the cellular level. In support of this inference, heat and growth arrest act synergistically to kill cells, and protein aggregation appears to occur more rapidly in protease mutants during growth arrest and correlates with the onset of cell death. Our findings suggest that protein aggregation is a major driver of aging and cell death during growth arrest, and that coordinated activity of the heat-shock response is required to ensure ongoing protein quality control in the absence of growth.

Sign in / Sign up

Export Citation Format

Share Document