Hsp100 Molecular Chaperone ClpB and Its Role in Virulence of Bacterial Pathogens

This review focuses on the molecular chaperone ClpB that belongs to the Hsp100/Clp subfamily of the AAA+ ATPases and its biological function in selected bacterial pathogens, causing a variety of human infectious diseases, including zoonoses. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections.     

Early-lactation extended pirlimycin therapy against naturally acquired Staphylococcus aureus intramammary infections in heifers: A randomized controlled trial

The primary objective of the current study was to evaluate cure rate following an early-lactation extended intramammary pirlimycin treatment on heifers naturally infected by Staphylococcus aureus. The secondary objective was to assess Petrifilm Staph Express (3M Microbiology, St. Paul, MN) count plate characteristics when used in a protocol for early-lactation detection of infected quarters in heifers. Milk samples were collected from heifers (n = 946) in the first few days following calving (mean = 5 d). Heifers with laboratory-confirmed S. aureus intramammary infection (n = 72) were randomly allocated into 2 groups. The treatment group (n = 54 quarters from 38 heifers) received an intramammary infusion of 50 mg of pirlimycin once per day for 8 consecutive days in infected quarters. The control group (n = 44 quarters from 34 heifers) did not receive any treatment. Treatment success was defined as having negative culture results for S. aureus in all 3 post-treatment quarter milk samples collected on d 17, 24, and 31 post-treatment. Treatment group mammary quarters showed a statistically significant higher cure rate (64.8%) compared with the control group (34.1%). A total of 38% of quarters identified as S. aureus-positive using the Petrifilm Staph Express count plate were in fact identified as non-aureus staphylococci on routine laboratory-based bacteriological culture. The current study demonstrates that a higher cure rate for S. aureus IMI can be achieved in dairy heifers if an extended treatment protocol is put in place soon after calving. Use of Petrifilm Staph Express count plate for identification of S. aureus-infected heifers could lead to unnecessary treatments because of false-positive results.     

温度、保湿时间及菌龄对扩展青霉 H1侵染柑橘能力的影响

近年来,由扩展青霉(Penicillium expansum)引起的柑橘病害日益严重,目前对于柑橘采后病原菌侵染的研究主要以指状青霉(P.digitatum)和意大利青霉(P.italicum)为主,而对P.expansum侵染柑橘条件的研究还未见相关文献报道。作者以实验室前期筛选鉴定的P.expansum H1为研究对象,研究了不同温度、保湿时间和菌龄对P.expansum H1侵染柑橘的影响,结果表明,P.expansum H1在25℃时潜育期最短,侵染能力最强,4℃时P.expansum H1侵染能力受到抑制;保湿时间越长,越有利于P.expansum H1侵染柑橘;菌龄也会影响P.expansum H1侵染柑橘,不同菌龄的P.expansum H1侵染能力高低排序为:培养7 d培养11 d培养15 d培养9 d培养3 d。     

Liver-Resident Memory CD8+ T Cells: Possible Roles in Chronic HBV Infection

Achieving a functional cure for chronic hepatitis B virus (HBV) infection or complete elimination of HBV covalently closed circular DNA (cccDNA) has been challenging in the treatment of patients with chronic HBV infection. Although novel antivirals are being investigated, improving HBV-specific adaptive immune responses is also important for durable viral clearance. Tissue-resident memory CD8⁺ T (T_RM) cells were recently reported as a T-cell population that resides in peripheral tissues and does not recirculate. T_RM cells have been studied in the livers of mice and humans. Liver T_RM cells have distinct characteristics compared to T cells in peripheral blood or other tissues, which may be associated with the unique microenvironment of the liver. In this review, we describe the characteristics of liver T_RM cells and their implications in chronic HBV infection. We emphasize that liver T_RM cells can be an immunotherapeutic target for the treatment of chronic HBV infection.     

Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain–Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.     

Bimetallic CuCo2S4 Nanozymes with Enhanced Peroxidase Activity at Neutral pH for Combating Burn Infections

Peroxidase-mimicking nanozymes that can generate toxic hydroxyl radicals (^.OH) hold great promise as antibacterial alternatives. However, most of them display optimal performance under strongly acidic conditions (pH 3–4), and are thus not feasible for many medical uses, including burn infections with a wound pH close to neutral. Herein, we report a copper-based nanozyme (CuCo₂S₄) that exhibits intrinsic peroxidase-like activity and can convert H₂O₂ into ^.OH at neutral pH. In particular, bimetallic CuCo₂S₄ nanoparticles (NPs) exhibited enhanced peroxidase-like activity and antibacterial capacity, superior to that of the corresponding monometallic CuS and CoS NPs. The CuCo₂S₄ nanozymes possessed excellent ability to kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, this CuCo₂S₄ nanozymes could effectively disrupt MRSA biofilms in vitro and accelerate MRSA-infected burn healing in vivo. This work provides a new peroxidase mimic to combat bacteria in neutral pH milieu and this CuCo₂S₄ nanozyme could be a promising antibacterial agent for the treatment of burn infections.     

Airborne spread of expiratory droplet nuclei between the occupants of indoor environments: A review

This article reviews past studies of airborne transmission between occupants in indoor environments, focusing on the spread of expiratory droplet nuclei from mouth/nose to mouth/nose for non‐specific diseases. Special attention is paid to summarizing what is known about the influential factors, the inappropriate simplifications of the thermofluid boundary conditions of thermal manikins, the challenges facing the available experimental techniques, and the limitations of available evaluation methods. Secondary issues are highlighted, and some new ways to improve our understanding of airborne transmission indoors are provided. The characteristics of airborne spread of expiratory droplet nuclei between occupants, which are influenced correlatively by both environmental and personal factors, were widely revealed under steady‐state conditions. Owing to the different boundary conditions used, some inconsistent findings on specific influential factors have been published. The available instrumentation was too slow to provide accurate concentration profiles for time‐dependent evaluations of events with obvious time characteristics, while computational fluid dynamics (CFD) studies were mainly performed in the framework of inherently steady Reynolds‐averaged Navier‐Stokes modeling. Future research needs in 3 areas are identified: the importance of the direction of indoor airflow patterns, the dynamics of airborne transmission, and the application of CFD simulations.     

Hand hygiene and surface cleaning should be paired for prevention of fomite transmission

Touching contaminated surfaces might lead to the spread of pathogens, that is, the fomite transmission route. Although hand- and surface-hygiene practices are potentially important non-pharmaceutical interventions for the fomite route, the two interventions have been mostly studied separately in the literature. In this study, we develop a new conceptual model based on the law of mass action, analyze the temporal diffusion of contaminated surfaces and hands, and verify the model with simulations in an assumed norovirus outbreak in a buffet restaurant. A quantitative hygiene criterion is developed for the required frequency of surface disinfection and hand hygiene to control the fomite transmission in indoor environments. To eliminate surface contaminations, the product of pathogen-removal rates (including hygiene and natural death) on hands and surfaces must be no smaller than that of the human hand and surface contact frequency (ie, the net removal product must be non-negative). When the net removal product is negative, the number of contaminated surfaces and hands would show a logistic growth trend and finally approach the equilibrium. Our approach sheds light into how to optimize the combined use of hand hygiene and environmental decontamination for the best effectiveness under different settings.     

Design of novel urogenital pharmabiotic formulations containing lactobacilli,salivaricin CRL 1328 and non-microbial compounds with different functionalities

Context: The administration of pharmabiotics is a promising alternative to antimicrobial drugs for the treatment and/or prevention of female urogenital infections.

Objective: To design pharmabiotic formulations including bioactive ingredients of microbial origin combined with non-microbial substances and then to evaluate the stability of the combinations during freeze-drying and storage.

Materials and methods: Different formulations including Lactobacillus gasseri CRL 1263, Lactobacillus salivarius CRL 1328, salivaricin CRL 1328 (a bacteriocin) and non-microbial compounds (lactose, inulin and ascorbic acid) were assayed, and the ingredients were freeze-dried together or separately. The formulations were stored in gelatin capsules at 4?°C for 360?d.

Results: The viability of lactobacilli was affected to different extents depending on the strains and on the formulations assayed. L. salivarius and ascorbic acid were successfully combined only after the freeze-drying process. Salivaricin activity was not detected in formulations containing L. gasseri. However, when combined with ascorbic acid, lactose, inulin or L. salivarius, the bacteriocin maintained its activity for 360?d. The selected microorganisms proved to be compatible for their inclusion in multi-strain formulations together with lactose, inulin and ascorbic acid. Salivaricin could be included only in a L. salivarius CRL 1328 single-strain formulation together with non-microbial substances.

Conclusions: This study provides new insights into the design of urogenital pharmabiotics combining beneficial lactobacilli, salivaricin CRL 1328 and compounds with different functionalities.