Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era.

The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected. However, recent studies have pointed out that the proportion of non-essential antibiotic use in patients infected with SARS-CoV-2 remains high. Therefore, the silent pandemic of antibiotic resistance remains a pressing issue regardless of the present threats presented by the COVID-19 pandemic. To prevent or delay entry into the postulated post-antibiotic era, the long-term advocacy for the rational use of antibiotics, the optimization of infection control procedures, and the development of new antibacterial agents and vaccines should be underscored as vital practices of the antibacterial toolbox. Recently, the development of vaccines and monoclonal antibodies has gradually received attention following the advancement of biotechnology as well as enhanced drug discovery and development in cancer research. Although decent progress has been made in laboratory-based research and promising results have been obtained following clinical trials of some of these products, challenges still exist in their widespread clinical applications. This article describes the current advantages of antibacterial monoclonal antibodies, the development of associated clinical trials, and some perceived future perspectives and challenges. Further, we anticipate the development of more therapeutic agents to combat drug-resistant bacterial infections as well as to increase the resilience of current or novel agents/strategies.

Pantailocins: phage-derived bacteriocins from Pantoea ananatis and Pantoea stewartii subsp. indologenes.

IMPORTANCE: Phage-derived bacteriocins (tailocins) are ribosomally synthesized structures produced by bacteria in order to provide advantages against competing strains under natural conditions. Tailocins are highly specific in their target range and have proven to be effective for the prevention and/or treatment of bacterial diseases under clinical and agricultural settings. We describe the discovery and characterization of a new tailocin locus encoded within genomes of Pantoea ananatis and Pantoea stewartii subsp. indologenes, which may enable the development of tailocins as preventative treatments against phytopathogenic infection by these species.

RpoS contributes in a host-dependent manner to Salmonella colonization of the leaf apoplast during plant disease.

Contaminated fresh produce has been routinely linked to outbreaks of Salmonellosis. Multiple studies have identified Salmonella enterica factors associated with successful colonization of diverse plant niches and tissues. It has also been well documented that S. enterica can benefit from the conditions generated during plant disease by host-compatible plant pathogens. In this study, we compared the capacity of two common S. enterica research strains, 14028s and LT2 (strain DM10000) to opportunistically colonize the leaf apoplast of two model plant hosts Arabidopsis thaliana and Nicotiana benthamiana during disease. While S. enterica 14028s benefited from co-colonization with plant-pathogenic Pseudomonas syringae in both plant hosts, S. enterica LT2 was unable to benefit from Pto co-colonization in N. benthamiana. Counterintuitively, LT2 grew more rapidly in ex planta N. benthamiana apoplastic wash fluid with a distinctly pronounced biphasic growth curve in comparison with 14028s. Using allelic exchange, we demonstrated that both the N. benthamiana infection-depedent colonization and apoplastic wash fluid growth phenotypes of LT2 were associated with mutations in the S. enterica rpoS stress-response sigma factor gene. Mutations of S. enterica rpoS have been previously shown to decrease tolerance to oxidative stress and alter metabolic regulation. We identified rpoS-dependent alterations in the utilization of L-malic acid, an abundant carbon source in N. benthamiana apoplastic wash fluid. We also present data consistent with higher relative basal reactive oxygen species (ROS) in N. benthamiana leaves than in A. thaliana leaves. The differences in basal ROS may explain the host-dependent disease co-colonization defect of the rpoS-mutated LT2 strain. Our results indicate that the conducive environment generated by pathogen modulation of the apoplast niche can vary from hosts to host even with a common disease-compatible pathogen.

Pseudomonas alliivorans sp. nov., a plant-pathogenic bacterium isolated from onion foliage in Georgia, USA.

This study provides a taxonomic characterization of three bacterial strains isolated from onion seedlings in Georgia USA. Yellow-colored colonies were isolated, and a diffusible fluorescent pigment was visible under ultraviolet light on King's medium B. Preliminary analysis of the basic phenotype tests and 16S rRNA gene sequence analysis indicated the onion strains were closely related to Pseudomonas viridiflava with the highest similarity to P. viridiflava DSM 6694T (99.6%). The phylogenomic analyses based on whole genome sequences showed that the onion strains formed a separate monophyletic clade from other species with P. viridiflava as the closest neighbor. When the onion strains and the P. viridiflava type strain were compared, the average nucleotide identity values was 91.6%. Additionally, the digital DNA-DNA hybridization values of the onion strains were 45.8% or less when compared to the type strains of their close relatives, including P. viridiflava. In addition, biochemical, physiological features, and cellular fatty acid compositions were determined for a polyphasic taxonomic analysis. The results supported that the three onion strains represented a novel Pseudomonas species. We propose a new species as Pseudomonas alliivorans sp. nov., with 20GA0068T (=LMG 32210T = CFBP 8885T) as the type strain. The DNA G + C content of the strain 20GA0068T is 59.1 mol%.

Pseudomonas capsici sp. nov., a plant-pathogenic bacterium isolated from pepper leaf in Georgia, USA.

Three phytopathogenic bacterial strains (Pc19-1T, Pc19-2 and Pc19-3) were isolated from seedlings displaying water-soaked, dark brown-to-black, necrotic lesions on pepper (Capsicum annuum) leaves in Georgia, USA. Upon isolation on King's medium B, light cream-coloured colonies were observed and a diffusible fluorescent pigment was visible under ultraviolet light. Analysis of their 16S rRNA gene sequences showed that they belonged to the genus Pseudomonas, with the highest similarity to Pseudomonas cichorii ATCC 10857T (99.7 %). The fatty acid analysis revealed that the majority of the fatty acids were summed feature 3 (C16  :  1 ω7c/C16  :  1 ω6c), C16  :  0 and summed feature 8 (C18  :  1 ω7c/C18  :  1 ω6c). Phylogenomic analyses based on whole genome sequences demonstrated that the pepper strains belonged to the Pseudomonas syringae complex with P. cichorii as their closest neighbour, and formed a separate monophyletic clade from other species. Between the pepper strains and P. cichorii, the average nucleotide identity values were 91.3 %. Furthermore, the digital DNA-DNA hybridization values of the pepper strains when compared to their closest relatives, including P. cichorii, were 45.2 % or less. In addition, biochemical and physiological features were examined in this study and the results indicate that the pepper strains represent a novel Pseudomonas species. Therefore, we propose a new species Pseudomonas capsici sp. nov., with Pc19-1T (=CFBP 8884T=LMG 32209T) as the type strain. The DNA G+C content of the strain Pc19-1T is 58.4 mol%.

Beyond surge: Coping with mass burn casualty in the closest hospital to the Formosa Fun Coast Dust Explosion.

PURPOSE: To provide an insight into the challenges faced by the closest hospital to the Formosa Fun Coast Dust Explosion (FFCDE) disaster scene, and to examine how the hospital staff adapted to cope with the mass burn casualty (MBC) in their overcrowded emergency department (ED) after the disaster. MATERIAL AND METHODS: The critical incident technique was used for the investigation. Data was gathered through in-depth individual interviews with 15 key participants in this event. The interview data was combined with the medical records of the FFCDE patients and admission logs to build a detailed timeline of ED workload. Process tracing analysis was used to evaluate how the ED and other units adapted to deal with actual and potential bottlenecks created by the patient surge. RESULTS: Fifty-eight burn patients were treated and registered in approximately six hours while the ED managed 43 non-FFCDE patients. Forty-four patients with average total body surface area burn 51.3% were admitted. Twenty burn patients were intubated. The overwhelming demand created shortages primarily of clinicians, ED space, stretchers, ICU beds, and critical medical materials for burn care. Adaptive activities for the initial resuscitation are identified and synthesized into three typical adaptation patterns. These adaptations were never previously adopted in ED normal practices for daily surge nor in periodical exercises. The analysis revealed adaptation stemmed from the dynamic re-planning and coordination across roles and units and the anticipation of bottlenecks ahead. CONCLUSION: In the hospital closest to the FFCDE disaster scene, it caused an overwhelming demand in an already crowded, beyond-nominal-capacity ED. This study describes how the hospital mobilized and reconfigured response capacity to cope with overload, uncertainty, and time pressure. These findings support improving disaster planning and preparedness for all healthcare entities through organizational support for adaptation and routine practice coping with unexpected scenarios.

TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and Central Nerve System.

BACKGROUND/AIMS: Acupuncture involves inserting a fine needle into a specific point, often called an acupoint, thereby initiating a therapeutic effect accompanied by phenomena such as soreness, heaviness, fullness, and numbness. Acupoints are characterized as points located in deep tissues with abundant sensory nerve terminals, which suggests that there is a strong relationship between acupoints and peripheral sensory afferents. In this study, we determined whether manual acupuncture (MA) or different frequencies of electroacupuncture (EA) share similar mechanisms for activating excitatory neurotransmission. METHODS: We performed MA or EA at acupoint ST36 and we also used western blot and immunostaining techniques to determine neural changes at the peripheral dorsal root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels. RESULTS: Our results show that either MA or EA at the ST36 acupoint significantly increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K, pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC-SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor (pNMDA) and pCaMKIIα (but not pNR2B, pCaMKIIδ, or pCaMKIIγ) also increased. These molecules could not increase in the DRG and SC-SSC of TRPV1-/-mice. CONCLUSION: Our data demonstrates that both MA and EA can activate excitatory signals in either peripheral or central levels. We also define that TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1-pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies the real clinical significance.