scholarly journals Antibacterial Peptide Nucleic Acids—Facts and Perspectives

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 559 ◽  
Author(s):  
Monika Wojciechowska ◽  
Marcin Równicki ◽  
Adam Mieczkowski ◽  
Joanna Miszkiewicz ◽  
Joanna Trylska
Keyword(s):  
Peptide Nucleic Acid ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antibacterial Studies ◽  
Compound Libraries ◽  
Alternative Approach ◽  
The Common ◽  
Time Required ◽  
Antibiotic Discovery

Antibiotic resistance is an escalating, worldwide problem. Due to excessive use of antibiotics, multidrug-resistant bacteria have become a serious threat and a major global healthcare problem of the 21st century. This fact creates an urgent need for new and effective antimicrobials. The common strategies for antibiotic discovery are based on either modifying existing antibiotics or screening compound libraries, but these strategies have not been successful in recent decades. An alternative approach could be to use gene-specific oligonucleotides, such as peptide nucleic acid (PNA) oligomers, that can specifically target any single pathogen. This approach broadens the range of potential targets to any gene with a known sequence in any bacterium, and could significantly reduce the time required to discover new antimicrobials or their redesign, if resistance arises. We review the potential of PNA as an antibacterial molecule. First, we describe the physicochemical properties of PNA and modifications of the PNA backbone and nucleobases. Second, we review the carriers used to transport PNA to bacterial cells. Furthermore, we discuss the PNA targets in antibacterial studies focusing on antisense PNA targeting bacterial mRNA and rRNA.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

scholarly journals Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR)

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Najwan Jubair ◽  
Mogana Rajagopal ◽  
Sasikala Chinnappan ◽  
Norhayati Binti Abdullah ◽  
Ayesha Fatima
Keyword(s):  
Secondary Metabolites ◽  
Plant Secondary Metabolites ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Resistance Strategies ◽  
Microbial Infections ◽  
Ancient Times ◽  
Antibiotic Discovery

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

scholarly journals Tigecycline: pharmacological concerns and resistance

2020 ◽  
Vol 9 (8) ◽  
pp. 1296
Author(s):  
Rama Paudel ◽  
Hari P. Nepal
Keyword(s):  
Side Effects ◽  
Ribosomal Subunit ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Skin Infections ◽  
Multidrug Resistant Bacteria ◽  
Enhanced Expression ◽  
The Common ◽  
Semisynthetic Derivative ◽  
Abdominal Infections

Tigecycline, a semisynthetic derivative of minocycline, has a broad spectrum of activity against both gram positive and gram negative multidrug resistant bacteria.  The drug acts on 30S ribosomal subunit and inhibits protein synthesis. Since the drug has excellent tissue distribution, it is very useful for treatment of skin infections, intra-abdominal infections and pneumonia. Side effects of the drug are usually mild. The common side effects include nausea and vomiting. The exact mechanism of resistance remains unclear. However, resistance mediated by enhanced expression of resistance nodulation cell division (RND) type efflux pumps is one of the most frequently reported mechanisms. Resistance has been observed worldwide. However, the rate of resistance is low.

scholarly journals Toward Autonomous Antibiotic Discovery

mSystems ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Cesar de la Fuente-Nunez
Keyword(s):  
Molecular Diversity ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Natural World ◽  
Resistant Bacteria ◽  
Computational Power ◽  
Molecular Scaffolds ◽  
Life Saving ◽  
Antibiotic Discovery ◽  
Global Health Challenge

ABSTRACT Machines hold the potential to replace humans in many societal endeavors, and drug discovery is no exception. Antibiotic innovation has been stalled for decades, which has coincided with an alarming increase in multidrug-resistant bacteria. Since the beginning of the antibiotic era, the natural world has been our greatest innovator, giving rise to nearly all antibiotics available today. As mere observers of the vast molecular diversity produced by Earth’s organisms, we have perfected the art of isolating novel chemistries with life-saving antimicrobial properties. However, today we are at a crossroads, as no new molecular scaffolds have been discovered for decades. We may need to look beyond the natural world into the virtual dimension for solutions and harness present-day computational power to help solve the grand global health challenge of antibiotic resistance. Computer-made drugs may enable the discovery of unprecedented functions in biological systems and help replenish our arsenal of effective antibiotics.

The application of cell-penetrating-peptides in antibacterial agents

2021 ◽  
Vol 28 ◽  
Author(s):  
Hangfei Chen ◽  
Dheerendranath Battalapalli ◽  
Mohamed S. Draz ◽  
Pengfei Zhang ◽  
Zhi Ruan
Keyword(s):  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Cell Penetrating Peptides ◽  
Resistant Bacteria ◽  
Full Potential ◽  
Bacterial Cells ◽  
Effective Prevention ◽  
Cell Penetrating ◽  
Low Toxicity

: Multidrug resistance in bacteria is a major threat to global health and the effective prevention and treatment of infections. The urgent need for novel antimicrobial agents, together with the increasing challenges in discovering and developing effective antibiotics, has inspired new approaches and strategies to circumvent antibiotic resistance. Despite this effort, the difficulty in cell-penetration and delivery of antibiotics into bacterial cells remains the bottleneck for both traditional and non-traditional antibacterial agents to realize their full potential. Recently, cell-penetrating peptides (CPPs) have attracted considerable attention as low-toxicity carriers, promising to improve the low biological activity of traditional antimicrobial agents. CPPs are now extensively used to deliver various antibiotics, including recently developed agents such as antisense oligonucleotides (ASOs). The conjugation of CPPs to antimicrobial peptides (AMPs) can also greatly enhance antibacterial activity and may present an effective approach to developing novel antimicrobial agents. This review discusses the characteristics, designing strategies, and recent progress in the development and application of antimicrobial CPPs as potent antibacterial agents against multidrug-resistant bacteria.

scholarly journals Colistin`s Dark Face. Resurrection of Polymyxin Antibiotics and Alternative Strategies

2017 ◽  
Vol 1 (1) ◽  
Keyword(s):  
Critically Ill ◽  
Common Sense ◽  
Critically Ill Patients ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Surgical Patient ◽  
Alternative Strategies ◽  
New Antibiotics ◽  
Polymyxin E ◽  
The Common

Due to the lack of new antibiotics for the treatment of critically ill patients with multidrug-resistant bacteria, interest on “old” antibiotics like colistin (polymyxin E) re-emerged. This polymyxin has gained an important role as salvage therapy for patients infected with microorganisms susceptible only to colistin. It is important to know the dark face of colistin referring here to its important toxicity, often lethal, especially in critically ill patients. Given its rarity we briefly mentioned a case of profound encephalopathy in a post-surgical patient who recovered completely after stopping the drug. In addition, its variable pharmacokinetics make it very difficult to establish an effective regimen, most of which is infratherapeutic and with the limitation of its toxicity, which is a terrible problem for humanity. The common sense of the clinician and the birth of new antibiotics, as an alternative strategy, represent a hope to eradicate multiresistance.

scholarly journals Function and Inhibitory Mechanisms of Multidrug Efflux Pumps

2021 ◽  
Vol 12 ◽  
Author(s):  
Kunihiko Nishino ◽  
Seiji Yamasaki ◽  
Ryosuke Nakashima ◽  
Martijn Zwama ◽  
Mitsuko Hayashi-Nishino
Keyword(s):  
Efflux Pump ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Inhibitory Mechanisms ◽  
Multidrug Efflux Pumps ◽  
Multiple Antibiotics

Multidrug efflux pumps are inner membrane transporters that export multiple antibiotics from the inside to the outside of bacterial cells, contributing to bacterial multidrug resistance (MDR). Postgenomic analysis has demonstrated that numerous multidrug efflux pumps exist in bacteria. Also, the co-crystal structural analysis of multidrug efflux pumps revealed the drug recognition and export mechanisms, and the inhibitory mechanisms of the pumps. A single multidrug efflux pump can export multiple antibiotics; hence, developing efflux pump inhibitors is crucial in overcoming infectious diseases caused by multidrug-resistant bacteria. This review article describes the role of multidrug efflux pumps in MDR, and their physiological functions and inhibitory mechanisms.

scholarly journals Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter Baumannii

2021 ◽  
Author(s):  
Xi Chen ◽  
Miao Liu ◽  
Pengfei Zhang ◽  
Miao Xu ◽  
Weihao Yuan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Galleria Mellonella ◽  
Volume Ratio ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Bacterial Cells ◽  
Strain Specificity ◽  
Drug Resistant Bacteria

Bacteriophage-encoded depolymerases are responsible for degrading capsular polysaccharides (CPS), lipopolysaccharides (LPS) and exopolysachcharides (EPS) of the host bacteria during phage invasion. They have been considered as promising antivirulence agents in controlling bacterial infections, including those caused by drug-resistant bacteria. This feature inspires a hope of utilizing these enzymes to disarm the polysaccharide capsid of the bacterial cells, which then strengthens the action of antibiotics. Here we have identified, cloned, and expressed a depolymerase Dpo71 from a bacteriophage specific for the gram-negative (G-ve) bacterium Acinetobacter baumannii in the heterologous host E. coli. Dpo71 sensitizes the multidrug-resistant (MDR) A. baumannii to the host immune attack, and also acts as an adjuvant to assist or boost the action of antibiotics, for example colistin. Specifically, Dpo71 at 10 µg/ml enables a complete bacterial eradication by human serum at 50% volume ratio. Dpo71 inhibits biofilm formation and disrupts the pre-formed biofilm. Combination of Dpo71 could significantly enhance the antibiofilm activity of colistin, and improve the survival rate of A. baumannii infected Galleria mellonella. Dpo71 retains the strain-specificity of the parent phage from which Dpo71 is derived: the phage-sensitive A. baumannii strains respond to Dpo71 treatment, whereas the phage-insensitive strains do not. This indicates that Dpo71 indeed is responsible for the host specificity of bacteriophages. In summary, our work demonstrates the feasibility of using recombinant depolymerases as an antibiotic adjuvants to supplement the development of new antibacterials and to battle against MDR pathogens.

scholarly journals Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus

2007 ◽  
Vol 51 (4) ◽  
pp. 1268-1273 ◽  
Author(s):  
Judy N. Chin ◽  
Michael J. Rybak ◽  
Chrissy M. Cheung ◽  
Paul B. Savage
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Curve Analysis ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Inoculum Effect ◽  
Kill Curve ◽  
Time Required ◽  
Time Kill

ABSTRACT The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log10-CFU/ml starting inoculum, whereas it was ≥24 h with a 8- to 9-log10-CFU/ml starting inoculum with 10× the MIC (P ≤ 0.001). A concentration-dependent PAE was demonstrated with CSA-13, nearly doubling from 2× to 4× the MIC (P = 0.03). With respect to the CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference in the log10 CFU/ml at 24 h for the majority of the organisms tested. However, early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain (2002) when CSA-13 was tested in combination with gentamicin, while early additivity was demonstrated against all of the other organisms.

scholarly journals Antimicrobials Functioning through ROS-Mediated Mechanisms: Current Insights

2021 ◽  
Vol 10 (1) ◽  
pp. 61
Author(s):  
Ankita Vaishampayan ◽  
Elisabeth Grohmann
Keyword(s):  
Oxidative Stress ◽  
Antibiotic Resistance ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Multidrug Resistant ◽  
Oxidation Potential ◽  
Resistant Bacteria ◽  
Oxygen Species ◽  
Bacterial Cells ◽  
Alternative Antimicrobials

Antibiotic resistance and infections caused by multidrug-resistant bacteria are global health concerns. Reducing the overuse and misuse of antibiotics is the primary step toward minimizing the antibiotic resistance crisis. Thus, it is imperative to introduce and implement novel antimicrobial strategies. Recently, several alternative antimicrobials targeting oxidative stress in bacteria have been studied and shown to be promising. Oxidative stress occurs when bacterial cells fail to detoxify the excessive reactive oxygen species (ROS) accumulated in the cells. Bacteria deploy numerous defense mechanisms against oxidative stress. The oxidative stress response is not essential for the normal growth of bacteria, but it is crucial for their survival. This toxic oxidative stress is created by the host immune response or antimicrobials generating ROS. ROS possess strong oxidation potential and cause serious damage to nucleic acids, lipids, and proteins. Since ROS-based antimicrobials target multiple sites in bacteria, these antimicrobials have attracted the attention of several researchers. In this review, we present recent ROS-based alternative antimicrobials and strategies targeting oxidative stress which might help in mitigating the problem of antibiotic resistance and dissemination.

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