SUMMARY: Despite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host’s immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their in vivo PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the in vitro PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, Klebsiella pneumoniae , Acinetobacter baumannii complex, Pseudomonas aeruginosa , and Escherichia coli , specific data on in vivo PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.

Microalgae are the primary producers in aquatic ecosystems, while simultaneously playing a vital role in various industrial sectors. Despite their significant ecological and bioeconomic importance, the impacts of oxidative stress on their populations remain poorly understood. In this mini-review, we summarize recent advancements in understanding oxidative stress modulation in microalgae, with a focus on responses to climate change-related stressors. Additionally, we compare the valuable insights obtained from multi-omics studies on specific biochemical pathways and genes, correlating the responses and mechanisms by which microalgae respond to oxidative stress among different species.

Vibrio harveyi, a significant opportunistic marine pathogen, has been a challenge to the aquaculture industry, leading to severe economical and production losses. Phage therapy has been an auspicious approach in controlling such bacterial infections in the era of antimicrobial resistance. In this study, we isolated and fully characterized a novel strain-specific phage, vB_VhaS_MAG7, which infects V. harveyi MM46, and tested its efficacy as a therapeutic agent in challenged gilthead seabream larvae. vB_VhaS_MAG7 is a tailed bacteriophage with a double-stranded DNA of 49,315 bp. No genes linked with virulence or antibiotic resistance were harbored in the genome. The phage had a remarkably large burst size of 1393 PFU cell⁻¹ and showed strong lytic ability in in vitro assays. When applied in phage therapy trials in challenged gilthead seabream larvae, vB_VhaS_MAG7 was capable of improving the survival of the larvae up to 20%. Due to its distinct features and safety, vB_VhaS_MAG7 is considered a suitable candidate for applied phage therapy.

With the aim to produce functional dairy products enriched with polyunsaturated fatty acids (PUFA) by using feed supplements, radical changes could occur in the rumen microbiome. This work investigated the alterations of the rumen bacteriome of goats fed with PUFA-rich marine microalgae Schizochytrium spp. For the trial, twenty-four goats were divided into four homogenous clusters (six goats/treatment) according to their fat-corrected (4%) milk yield, body weight, and age; they were individually fed with alfalfa hay and a concentrate (F/C = 50/50). The concentrate of the control group (CON) contained no microalgae, while those of the treated groups were supplemented daily with 20 (ALG20), 40 (ALG40), and 60 g (ALG60) of Schizochytrium spp./goat. Rumen fluid samples were collected using a stomach tube during the 20th and 40th days of the experiment. The microbiome analysis using a 16S rRNA sequencing platform revealed that Firmicutes were decreased in microalgae-fed goats, while Bacteroidetes showed a tendency to increase in the ALG40 group due to the enhancement of Prevotellaceae. Cellulolytic bacteria, namely Treponema bryantii, Ruminococcus gauvreauii, R. albus, and R. flavefaciens, were decreased in the ALG40 group, resulting in an overall decrease of cellulase activity. In contrast, the amylolytic potential was significantly enhanced due to an upsurge in Ruminobacter amylophilus, Succinivibrio dextrinosolvens, and Fretibacterium fastidiosum populations. In conclusion, supplementing goats’ diets with 20 g Schizochytrium spp. could be considered a sustainable and efficient nutritional strategy to modulate rumen microbiome towards the development of dairy products enriched with bioactive compounds, while higher levels induced substantial shifts in determinant microbes’ populations.