Broad Antibacterial Spectrum Research Articles

Expression of secreted antimicrobial peptide in a marine diatom—Phaeodactylum tricornutum

Antimicrobial peptides (AMPs) are small-molecule polypeptides that occur widely in nature, have a broad antibacterial spectrum, and do not induce drug resistance in bacteria. Therefore, they are potential substitutes for antibiotics. However, there have been few reports of the production of the AMPs secreted by diatoms. Phaeodactylum tricornutum is a model diatom species for which protocols for its transformation are well established, and it can be directly used as fish and shrimp bait. In this study, we used P. tricornutum as a cell factory to produce secreted AMPs extracellularly. We also constructed an expression vector containing the secretory promoter and signal peptide of the Scygonadin gene, and successfully expressed AMPs in P. tricornutum, confirmed at the levels of DNA, RNA, and protein. Bacteriostatic experiments showed that the secreted AMPs exerted an obvious antibacterial effect on Kocuria sp. and Trelief5α Chemical Competent Cells. This study demonstrates that P. tricornutum effectively expresses and secretes AMPs with obvious antibacterial effects.

A multifunctional cascade nanoreactor based on Fe-driven carbon nanozymes for synergistic photothermal/chemodynamic antibacterial therapy.

Healing bacterial chronic wounds caused by hyperglycemia is of great significance to protect the physical and mental health of diabetic patients. In this context, emerging chemodynamic therapy (CDT) and photothermal therapy (PTT) with broad antibacterial spectra and high spatiotemporal controllability have flourished. However, CDT was challenged by the near-neutral pH and inadequate H2O2 surrounding the chronic wound site, while PTT showed overheating-triggered side effects (e.g., damaging the normal tissue) and poor effects on thermotolerant bacterial biofilms. Therefore, we engineered an all-in-one glucose-responsive photothermal nanozyme, GOX/MPDA/Fe@CDs, consisting of glucose oxidase (GOX), Fe-doped carbon dots (Fe@CDs), and mesoporous polydopamine (MPDA), to efficiently treat chronic diabetic wound bacterial infections and eradicate biofilms without impacting the surrounding normal tissues. Specifically, GOX/MPDA/Fe@CDs produced a local temperature (∼ 45.0°C) to enhance the permeability of the pathogenic bacterium and its biofilm upon near-infrared (NIR) 808 nm laser irradiation, which was seized to initiate endogenous high blood glucose to activate the catalytic activity of GOX on the GOX/MPDA/Fe@CD surface to achieve the simultaneous self-supplying of H2O2 and H+, cascade catalyzing •OH production via a subsequent peroxidase-mimetic activity-induced Fenton/Fenton-like reaction. As such, the in vivo diabetic wound infected with methicillin-resistant Staphylococcus aureus was effectively healed after 12.0 days of treatment. This work was expected to provide an innovative approach to the clinical treatment of bacterially infected diabetic chronic wounds. STATEMENT OF SIGNIFICANCE: An all-in-one glucose-responsive photothermal nanozyme GOX/MPDA/Fe@CDs was constructed. Cascade nanozyme GOX/MPDA/Fe@CDs self-supply H2O2 and H+ to break H2O2 and pH limits to fight bacterial infections. Synergistic chemotherapy and photothermal therapy with nanozyme GOX/MPDA/Fe@CDs accelerates healing of biofilm-infected diabetic wounds.

Size-Controlled Ammonium-Based Homopolymers as Broad-Spectrum Antibacterials.

Ammonium group containing polymers possess inherent antimicrobial properties, effectively eliminating or preventing infections caused by harmful microorganisms. Here, homopolymers based on monomers containing ammonium groups were synthesized via Reversible Addition Fragmentation Chain Transfer Polymerization (RAFT) and evaluated as potential antibacterial agents. The antimicrobial activity was evaluated against Gram-positive (M. luteus and B. subtilis) and Gram-negative bacteria (E. coli and S. typhimurium). Three polymers, poly(diallyl dimethyl ammonium chloride), poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), and poly(vinyl benzyl trimethylammonium chloride), were examined to explore the effect of molecular weight (10 kDa, 20 kDa, and 40 kDa) on their antimicrobial activity and toxicity to mammalian cells. The mechanisms of action of the polymers were investigated with dye-based assays, while Scanning Electron Microscopy (SEM) showed collapsed and fused bacterial morphologies due to the interactions between the polymers and components of the bacterial cell envelope, with some polymers proving to be bactericidal and others bacteriostatic, while being non-hemolytic. Among all the homopolymers, the most active, non-Gram-specific polymer was poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), with a molecular weight of 40 kDa, with minimum inhibitory concentrations between 16 and 64 µg/mL, showing a bactericidal mode of action mediated by disruption of the cytoplasmic membrane. This homopolymer could be useful in biomedical applications such as surface dressings and in areas such as eye infections.

Antibacterial Activity of Thesium chinense Turcz Extract Against Bacteria Associated with Upper Respiratory Tract Infections.

The drug resistance of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae has become more and more serious, and it is urgent to seek new antibacterial drugs. In this study, Thesium chinense Turcz. extracts were tested for its potential antibacterial activities. T. chinense powder was extracted with 5 solvents of different polarity (ethyl alcohol, petroleum ether, ethyl acetate, n-butyl alcohol and double distilled water), and their antibacterial activities were tested. The Broth dilution method was used to evaluate the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of highly active plant extracts with a concentration of 1g/mL. The inhibitory activity of this extract on biofilm formation was investigated. Afterwards, we investigated its effect on the transcriptome of S. aureus. The ethanol extract coded as BRY, only inhibited S. aureus, whereas the ethyl acetate extract coded as BY2 showed inhibitory effect on all the tested bacteria. The MIC of BRY on S. aureus was 128 mg/mL, and the MBC was 512 mg/mL. The MIC of BY2 against S. aureus, S. pneumoniae, S. pyogenes and H. influenzae were 8 mg/mL, 4 mg/mL, 4 mg/mL, and 4 mg/mL, respectively. The MBC of BY2 for these four bacteria ranged from 4 to 256 mg/mL. Mechanism studies have shown that BRY and BY2 have an impact on anti-formation of biofilms at MIC concentrations. Transcriptome sequencing results showed that 531 genes were up-regulated and 340 genes showed down-regulated expression in S. aureus after BY2 treatment. BY2 has a broader antibacterial spectrum than BRY. Meanwhile, the inhibitory effect of BY2 on S. aureus is better than BRY. The mechanism of BY2 against S. aureus may relate to its inhibition of ribosome synthesis, restriction of key enzymes of citric acid cycle, decrease of pathogenicity and influence on biofilm formation. The results confirmed that BY2 was the main antibacterial part of T. chinense, which can be used as a source of antibacterial agents.

The bacterial culture of urine relevance in the complex treatment of incontinence in dogs

To date in Russian federation there is widespread in veterinary medicine to empiric prescription of broad-spectrum antibacterial drugs in the treatment of bacterial cystitis in dogs. The main danger of this approach is associated with the provocation of the development of antibiotic resistance of microorganisms, with the surgical treatment of animals in the active stage of the inflammatory process and associated complications, with the development of ascending infections of the urinary system. Very important for a positive clinical result in the treatment of dogs with urinary incontinence against the background of ureteral ectopia or urethral sphincter insufficiency has a compliance with the preanalytical rules when taking biomaterial (urine) for bacteriological examination by pyelocentesis or cystocentesis. So there is data how to obtaining a biomaterial and its laboratory research in this article. This article presents arguments to the feasibility and necessity of conducting a laboratory study of the bacterial composition of urine in the treatment of inflammatory diseases of the urinary system associated with urinary incontinence. This approach makes it possible to prevent the development of antibiotic resistance in bacteria, stop the actual infectious process and ensure high rates of treatment. Вacterial culture of urine is one of the most important tests to ensure the successful treatment of patients with such diseases. Also in analyzes results we can see the insufficiency and associated risks of broadspectrum antibacterial drugs’s "blind" prescription, which has negative affect for treatment

Recent advances on nanomaterials for antibacterial treatment of oral diseases

An imbalance of bacteria in oral environment can lead to a variety of oral diseases, such as periodontal disease, dental caries, and peri-implant inflammation. In the long term, in view of the increasing bacterial resistance, finding suitable alternatives to traditional antibacterial methods is an important research today. With the development of nanotechnology, antibacterial agents based on nanomaterials have attracted much attention in dental field due to their low cost, stable structures, excellent antibacterial properties and broad antibacterial spectrum. Multifunctional nanomaterials can break through the limitations of single therapy and have the functions of remineralization and osteogenesis on the basis of antibacterial, which has made significant progress in the long-term prevention and treatment of oral diseases. In this review, we have summarized the applications of metal and their oxides, organic and composite nanomaterials in oral field in recent five years. These nanomaterials can not only inactivate oral bacteria, but also achieve more efficient treatment and prevention of oral diseases by improving the properties of the materials themselves, enhancing the precision of targeted delivery of drugs and imparting richer functions. Finally, future challenges and untapped potential are elaborated to demonstrate the future prospects of antibacterial nanomaterials in oral field.

Complete Genome Sequence of Bacteriophage EO1, Which Infects Both Escherichia coli O157:H7 and Shigella.

The lytic bacteriophage EO1 has been newly isolated. This phage infects Escherichia coli O157:H7 and has a broad antibacterial spectrum, including against Shigella. The complete genome sequence of phage EO1 was determined; its full length is 166,941 bp, and it has a G+C content of 35.46%.

Therapeutic Peptides for Treatment of Lung Diseases: Infection, Fibrosis, and Cancer.

Various lung diseases endanger people's health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future.

Mycobacterial metabolic model development for drug target identification.

Antibiotic resistance is increasing at an alarming rate, and three related mycobacteria are sources of widespread infections in humans. According to the World Health Organization, Mycobacterium leprae, which causes leprosy, is still endemic in tropical countries; Mycobacterium tuberculosis is the second leading infectious killer worldwide after COVID-19; and Mycobacteroides abscessus, a group of non-tuberculous mycobacteria, causes lung infections and other healthcare-associated infections in humans. Due to the rise in resistance to common antibacterial drugs, it is critical that we develop alternatives to traditional treatment procedures. Furthermore, an understanding of the biochemical mechanisms underlying pathogenic evolution is important for the treatment and management of these diseases. In this study, metabolic models have been developed for two bacterial pathogens, M. leprae and My. abscessus, and a new computational tool has been used to identify potential drug targets, which are referred to as bottleneck reactions. The genes, reactions, and pathways in each of these organisms have been highlighted; the potential drug targets can be further explored as broad-spectrum antibacterials and the unique drug targets for each pathogen are significant for precision medicine initiatives. The models and associated datasets described in this paper are available in GigaDB, Biomodels, and PatMeDB repositories.

Isolation, Characterization and Antibacterial Activity of 4-Allylbenzene-1,2-diol from Piper austrosinense.

Isolation for antibacterial compounds from natural plants is a promising approach to develop new pesticides. In this study, two compounds were obtained from the Chinese endemic plant Piper austrosinense using bioassay-guided fractionation. Based on analyses of 1H-NMR, 13C-NMR, and mass spectral data, the isolated compounds were identified as 4-allylbenzene-1,2-diol and (S)-4-allyl-5-(1-(3,4-dihydroxyphenyl)allyl)benzene-1,2-diol. 4-Allylbenzene-1,2-diol was shown to have strong antibacterial activity against four plant pathogens, including Xanthomonas oryzae pathovar oryzae (Xoo), X. axonopodis pv. citri (Xac), X. oryzae pv. oryzicola (Xoc) and X. campestris pv. mangiferaeindicae (Xcm). Further bioassay results exhibited that 4-allylbenzene-1,2-diol had a broad antibacterial spectrum, including Xoo, Xac, Xoc, Xcm, X. fragariae (Xf), X. campestris pv. campestris (Xcc), Pectobacterium carotovorum subspecies brasiliense (Pcb) and P. carotovorum subsp. carotovorum (Pcc), with minimum inhibitory concentration (MIC) values ranging from 333.75 to 1335 μmol/L. The pot experiment showed that 4-allylbenzene-1,2-diol exerted an excellent protective effect against Xoo, with a controlled efficacy reaching 72.73% at 4 MIC, which was superior to the positive control kasugamycin (53.03%) at 4 MIC. Further results demonstrated that the 4-allylbenzene-1,2-diol damaged the integrity of the cell membrane and increased cell membrane permeability. In addition, 4-allylbenzene-1,2-diol also prevented the pathogenicity-related biofilm formation in Xoo, thus limiting the movement of Xoo and reducing the production of extracellular polysaccharides (EPS) in Xoo. These findings suggest the value of 4-allylbenzene-1,2-diol and P. austrosinense could be as promising resources for developing novel antibacterial agents.

Thymol-Decorated Gold Nanoparticles for Curing Clinical Infections Caused by Bacteria Resistant to Last-Resort Antibiotics.

Multidrug-resistant bacteria pose a tremendous challenge to public health worldwide. Many bacteria resistant to last-resort antibiotics due to antibiotic misuse have been recently reported, which may give rise to serious infections without effective treatment. Therefore, it is imperative to develop novel antimicrobial strategies. Natural phenols are known to increase bacterial membrane permeability and are potential candidates for the development of new antimicrobial agents. In this study, gold nanoparticles (Au NPs) carrying natural phenols were synthesized to combat bacteria resistant to last-resort antibiotics. Transmission electron microscopy, dynamic light scattering, zeta potential, and UV-visible spectra were used to characterize the synthesized Au NPs, which showed good monodispersity and uniform particle size. Evaluation of antibacterial activity using the broth microdilution method revealed that thymol-decorated gold nanoparticles (Thymol_Au NPs) had a broad antibacterial spectrum and higher bactericidal effects than last-resort antibiotics against last-resort-antibiotic-resistant bacteria. Considering the underlying antibacterial mechanism, the results showed that Thymol_Au NPs destroyed bacterial cell membranes. Further, Thymol_Au NPs were effective in treating mouse abdominal infections and exhibited acceptable biocompatibility without any significant toxicity in cell viability and histopathological assays, respectively, at most bactericidal concentrations. However, attention should be paid to changes in white blood cells, reticulocyte percentages, and superoxide dismutase activity during Thymol_Au NP treatment. In conclusion, Thymol_Au NPs have the potential for treating clinical infections caused by bacteria resistant to last-resort antibiotics. IMPORTANCE Excessive use of antibiotics can lead to bacterial resistance and the development of multidrug-resistant bacteria. Antibiotic misuse can also promote resistance against last-resort antibiotics. It is thus crucial to develop alternatives to antibiotics to retard the development of multidrug resistance. In recent years, the use of several nanodosage forms of antibacterial drugs has been investigated. These agents kill bacteria through a variety of mechanisms and avoid the problem of resistance. Among them, Au NPs, which are safer to use for medical applications than other metal nanoparticles, have attracted interest as potential antibacterial agents. To combat bacterial resistance to last-resort antibiotics and mitigate the problem of antimicrobial resistance, it is important and meaningful to develop antimicrobial agents based on Au NPs.

Recent progress of antibacterial hydrogels in wound dressings.

Hydrogels are essential biomaterials due to their favorable biocompatibility, mechanical properties similar to human soft tissue extracellular matrix, and tissue repair properties. In skin wound repair, hydrogels with antibacterial functions are especially suitable for dressing applications, so novel antibacterial hydrogel wound dressings have attracted widespread attention, including the design of components, optimization of preparation methods, strategies to reduce bacterial resistance, etc. In this review, we discuss the fabrication of antibacterial hydrogel wound dressings and the challenges associated with the crosslinking methods and chemistry of the materials. We have investigated the advantages and limitations (antibacterial effects and antibacterial mechanisms) of different antibacterial components in the hydrogels to achieve good antibacterial properties, and the response of hydrogels to stimuli such as light, sound, and electricity to reduce bacterial resistance. Conclusively, we provide a systematic summary of antibacterial hydrogel wound dressings findings (crosslinking methods, antibacterial components, antibacterial methods) and an outlook on long-lasting antibacterial effects, a broader antibacterial spectrum, diversified hydrogel forms, and the future development prospects of the field.

Cloning, recombinant expression, purification, and functional characterization of AGAAN antibacterial peptide.

A recombinant version of the AGAAN antimicrobial peptide (rAGAAN) was cloned, expressed, and purified in this study. Its antibacterial potency and stability in harsh environments were thoroughly investigated. A 15kDa soluble rAGAAN was effectively expressed in E. coli. The purified rAGAAN exhibited a broad antibacterial spectrum and was efficacious against seven Gram-positive and Gram-negative bacteria. The minimal inhibitory concentration (MIC) of rAGAAN against the growth of M. luteus (TISTR 745) was as low as 60µg/ml. Membrane permeation assay reveals that the integrity of the bacterial envelope is compromised. In addition, rAGAAN was resistant to temperature shock and maintained a high degree of stability throughout a reasonably extensive pH range. The bactericidal activity of rAGAAN ranged from 36.26 to 79.22% in the presence of pepsin and Bacillus proteases. Lower bile salt concentrations had no significant effect on the function of the peptide, whereas higher concentrations induced E. coli resistance. Additionally, rAGAAN exhibited minimal hemolytic activity against red blood cells. This study indicated that rAGAAN may be produced on a large scale in E. coli and that it had an excellent antibacterial activity and sufficient stability. This first work to express biologically active rAGAAN in E. coli yielded 8.01mg/ml at 16°C/150rpm for 18h in Luria Bertani (LB) medium supplemented with 1% glucose and induced with 0.5mM IPTG. It also assesses the interfering factors that influence the activity of the peptide, demonstrating its potential for research and therapy of multidrug-resistant bacterial infections.

Unraveling the molecular mechanism of type II topoisomerase poisons with magnetic tweezers.

Topoisomerases are an essential class of enzymes that resolve topological problems on DNA (e.g., supercoils, knots, and links) that arise during transcription, replication, and recombination. As part of their reaction cycle, type II topoisomerases transiently cleave double-stranded DNA and form a covalent protein-DNA cleavage complex. Typically, these cleavage complexes are tightly regulated in vivo because they are highly vulnerable and can generate cytotoxic DNA breaks, yet some of the most efficacious and broad-spectrum antibacterials are topoisomerase poisons that exploit this vulnerability by disrupting cleavage complex regulation. Due to their biological and clinical importance, the effects of these poisons have been studied extensively with a variety of in vitro ensemble assays. These assays have shown that antibacterials increase overall levels of cleavage complexes and inhibit enzyme activity. However, the kinetics of individual poisoned cleavage complexes under physiologically relevant conditions is unknown. Therefore, we carried out single-molecule magnetic tweezer measurements of E. coli topo IV activity on supercoiled DNA. In the presence of topoisomerase poisons, we observed long pauses in enzyme activity that correspond to poison-stabilized cleavage complexes. We studied the effects of DNA tension, as well as supercoil handedness and extent, determining poison on-rates, cleavage-complex lifetimes, and topoisomerase activity with several common antibacterials under physiologically relevant conditions. Together, these results provide new mechanistic insight into how topoisomerase poisons disrupt cleavage complex regulation that is likely to be relevant to their action in vivo.

Engineering core-shell chromium nanozymes with inflammation-suppressing, ROS-scavenging and antibacterial properties for pulpitis treatment.

Oral diseases are usually caused by inflammation and bacterial infection. Reactive oxygen species (ROS), which come from both autologous inflammation tissue and bacterial infection, play an important role in this process. Thus, the elimination of excessive intracellular ROS can be a promising strategy for anti-inflammatory treatment. With the rapid development of nanomedicines, nanozymes, which can maintain the intracellular redox balance and protect cells against oxidative damage, have shown great application prospects in the treatment of inflammation-related diseases. However, their performance in pulpitis and their related mechanisms have yet to be explored. Herein, we prepared dozens of metallic nanoparticles with core-shell structures, and among them, chromium nanoparticles (NanoCr) were selected for their great therapeutic potential for pulpitis disease. NanoCr showed a broad antibacterial spectrum and strong anti-inflammatory function. Antibacterial assays showed that NanoCr could effectively inhibit a variety of common pathogens of oral infection. In vitro experiments offered evidence of the multienzyme activity of NanoCr and its function in suppressing ROS-induced inflammation reactions. The experimental results show that NanoCr has optimal antibacterial and anti-inflammatory properties in in vitro cell models, showing great potential for the treatment of pulpitis. Therefore, the use of NanoCr could become a new therapeutic strategy for clinical pulpitis.

Peritonitis – Etiology and Treatment Options: A Systematic Review

Peritonitis is an infection with a substantial source of morbidity and death. The mortality rate is 10% to 60%. Its etiology may be infection of bacteria, viruses, or fungi. The objective of the current systematic review is to identify the causes of peritonitis and discuss available treatment options. A systematic review was conducted from the literature from January 2012 to December 2022. More than 60 articles were downloaded; after abstracting relevant information from the studies and assessing quality, data was synthesized and presented by PRISMA flow diagram. The most common cause was bacterial infection; followed by fungal and viral infections. Reported organisms were E. coli, Klebsiella spp., Streptococcus spp., M. tuberculosis, C. trachomatis, Pseudomonas spss., C. albicans, C. glabrata, C. krusei, Cryptococcus spp., and Aspergillus spp., and Feline-infectious-corona-virus. Empiric antibiotics therapy covers broad-spectrum antibacterials; antifungal and surgical interventions are treatment options. The acutely ill patient requires combined medical and surgical methods; culture sensitivity is highly advisable to reduce the chances of failure.

Antagonistic Potentiality of Actinomycete-Derived Extract with Anti-Biofilm, Antioxidant, and Cytotoxic Capabilities as a Natural Combating Strategy for Multidrug-Resistant ESKAPE Pathogens.

The global increase in multidrug-resistant (MDR) bacteria has inspired researchers to develop new strategies to overcome this problem. In this study, 23 morphologically different, soil-isolated actinomycete cultures were screened for their antibacterial ability against MDR isolates of ESKAPE pathogens. Among them, isolate BOGE18 exhibited a broad antibacterial spectrum, so it was selected and identified based on cultural, morphological, physiological, and biochemical characteristics. Chemotaxonomic analysis was also performed together with nucleotide sequencing of the 16S rRNA gene, which showed this strain to have identity with Streptomyces lienomycini. The ethyl acetate extract of the cell-free filtrate (CFF) of strain BOGE18 was evaluated for its antibacterial spectrum, and the minimum inhibitory concentration (MIC) ranged from 62.5 to 250 μg/ml. The recorded results from the in vitro anti-biofilm microtiter assay and confocal laser scanning microscopy (CLSM) of sub-MIC concentrations revealed a significant reduction in biofilm formation in a concentration-dependent manner. The extract also displayed significant scavenging activity, reaching 91.61 ± 4.1% and 85.06 ± 3.14% of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis( 3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), respectively. A promising cytotoxic ability against breast (MCF-7) and hepatocellular (HePG2) cancer cell lines was obtained from the extract with IC50 values of 47.15 ± 13.10 and 122.69 ± 9.12 μg/ml, respectively. Moreover, based on gas chromatography-mass spectrometry (GC-MS) analysis, nine known compounds were detected in the BOGE18 extract, suggesting their contribution to the multitude of biological activities recorded in this study. Overall, Streptomyces lienomycini BOGE18-derived extract is a good candidate for use in a natural combating strategy to prevent bacterial infection, especially by MDR pathogens.

Opportunistic Challenges of Computer-aided Drug Discovery of Lipopeptides: New Insights for Large Molecule Therapeutics.

Computer-aided drug designing is a promising approach to defeating the dry pipeline of drug discovery. It aims at reduced experimental efforts with cost-effectiveness. Naturally occurring large molecules with molecular weight higher than 500 Dalton such as cationic peptides, cyclic peptides, glycopeptides and lipopeptides are a few examples of large molecules which have successful applications as the broad spectrum antibacterial, anticancer, antiviral, antifungal and antithrombotic drugs. Utilization of microbial metabolites as potential drug candidates incur cost effectiveness through large scale production of such molecules rather than a synthetic approach. Computational studies on such compounds generate tremendous possibilities to develop novel leads with challenges to handle these complex molecules with available computational tools. The opportunities begin with the desired structural modifications in the parent drug molecule. Virtual modifications followed by molecular interaction studies at the target site through molecular modeling simulations and identification of structure-activity relationship models to develop more prominent and potential drug molecules. Lead optimization studies to develop novel compounds with increased specificity and reduced off targeting is a big challenge computationally for large molecules. Prediction of optimized pharmacokinetic properties facilitates development of a compound with lower toxicity as compared to the natural compounds. Generating the library of compounds and studies for target specificity and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) for large molecules are laborious and incur huge cost and chemical wastage through in-vitro methods. Hence, computational methods need to be explored to develop novel compounds from natural large molecules with higher specificity. This review article is focusing on possible challenges and opportunities in the pathway of computer-aided drug discovery of large molecule therapeutics.

Purification and characterization of a novel bacteriocin from Lactiplantibacillus plantarum Z057, and its antibacterial and antibiofilm activities against Vibrio parahaemolyticus

Vibrio parahaemolyticus and its biofilm threaten food safety and human health. Bacteriocins are known to inhibit various foodborne bacteria and their biofilms; however, few bacteriocins with antibiofilm activity against V. parahaemolyticus have been reported. Herein, a novel plantaricin Z057 from Lactiplantibacillus plantarum Z057 was extracted with ethyl acetate, purified by Sephadex LH-20 gel chromatography and reversed-phase high-performance liquid chromatography, and identified by nano-liquid chromatography coupled with tandem mass spectrometry. Its molecular mass and amino acid composition were 1272.61 Da and A-G-G-D-G-G-H-G-G-S-I-I-L-Y, respectively. Plantaricin Z057 presented a broad antibacterial spectrum against Gram-positive and Gram-negative pathogens. Moreover, it also exhibited excellent heat tolerance, maintained antibacterial activity at pH 2.0–4.0, and was susceptible to common proteases (pepsin, trypsin, papain, proteinase K). In addition, scanning electron microscopy revealed that plantaricin Z057 destroyed membrane integrity and caused cell deformation and cytoplasmic leakage. The crystal violet staining and XTT reduction assays revealed that plantaricin Z057 markedly decreased biofilm biomass and metabolic activity of V. parahemolyticus. Fluorescence microscopy showed that plantaricin Z057 efficiently inactivated sessile cells, and damaged integrated biofilm structure by reducing the extracellular polymer content. In summary, plantaricin Z057 exhibited significant potential for controlling V. parahaemolyticus and could be used in food production as a biological preservative.

1164. Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania

Abstract Background Antimicrobial resistance is an important cause of morbidity and mortality globally; low- and middle-income countries (LMICs) face an especially high burden. Ineffective antimicrobial prescriptions and use of broad-spectrum agents contribute to resistance. We describe antibacterial prescribing patterns in patients with febrile illnesses and bloodstream infections (BSI) in northern Tanzania. Methods We compared data from two hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), both enrolled febrile pediatric and adult inpatients in Moshi, Tanzania. Aerobic blood culture was obtained in all patients and standard methods were used to determine isolate antimicrobial susceptibility. To describe management of febrile illness, we analyzed antibacterial drug prescription prior to and after enrollment. Broad-spectrum antibacterials were categorized using published frameworks. Treatments were categorized as discordant if a blood culture isolate was not susceptible to the patient’s antibacterial regimen. We performed descriptive statistics and logistic regression to understand predictors of receiving an antibacterial. Results In total, 2,176 febrile inpatients were enrolled. Antibacterials were administered to 430 (42.0%) and 501 (45.1%) patients prior to enrollment, and 930 (89.1%) and 1,060 (93.6%) during admission in cohorts 1 and 2, respectively. Infancy and duration of fever were associated with higher antibacterial prescribing prior to enrollment (Table 2). Broad-spectrum antibacterials were administered to 548 (52.5%) in cohort 1 and 682 (60.2%) in cohort 2. Laboratory-confirmed bacteremia was detected in 87 (4%) patients. Susceptibility results were available in 73 patients; of these, 41 (56.2%) received discordant antibacterials. Conclusion Antibacterials were commonly administered for febrile illness in outpatient and inpatient settings; over half of patients received broad-spectrum antibacterials. A high proportion of patients with culture-positive BSI were treated with ineffective antimicrobials. Improved laboratory diagnostics for febrile illness, antimicrobial stewardship interventions, context-specific clinical guidelines, and provider education may improve prescribing practices. Disclosures Julian Hertz, MD, Roche Diagnostics: Grant/Research Support.