The coronavirus disease (COVID-19) threat is subsiding through extensive vaccination worldwide. However, the pandemic imposed major disruptions in global immunization programs and has aggravated the risks of vaccine-preventable disease (VPD) outbreaks. Particularly, lower-middle-income regions with minimal vaccine coverage and circulating vaccine-derived viral strains, such as polio, suffered additional burden of accumulated zero-dose children, further making them vulnerable to VPDs. However, there is no compilation of routine immunization disruptions and recovery prospects. There is a noticeable change in the routine vaccination coverage across different phases of the pandemic in six distinct global regions. We have summarized the impact of COVID-19 on routine global vaccination programs and also identified the prospects of routine immunization to combat COVID-like outbreaks.

Myxobacteria are natural predators of microorganisms and the subjects of concerted efforts to identify novel antimicrobial compounds. Myxobacterial predatory activity seems to require more than just the possession of specific antimicrobial metabolites. Thus a holistic approach to studying predation promises novel insights into antimicrobial action. Here we report the isolation of 113 myxobacteria from samples of soil taken from a range of habitats in mid Wales. Predatory activity of each isolate was quantified against a panel of clinically important prey organisms, including Klebsiella pneumoniae, Proteus mirabilis, Candida albicans, Enterococcus faecalis, and three species of Staphylococcus. Myxobacterial isolates exhibited a wide range of predation activity profiles against the panel of prey. Efficient predation of all prey by isolates within the collection was observed, with K. pneumoniae and C. albicans proving particularly susceptible to myxobacterial predation. Notably efficient predators tended to be proficient at predating multiple prey organisms, suggesting they possess gene(s) encoding a broad range killing activity. However, predatory activity was not congruent with phylogeny, suggesting prey range is subject to rapid specialisation and/or lateral gene transfer. The broad but patchy prey ranges observed for natural myxobacterial isolates also implies multiple (potentially overlapping) genetic determinants are responsible for dictating predatory activity.

Corallococcus is an abundant genus of predatory soil myxobacteria, containing two species, C. coralloides (for which a genome sequence is available) and C. exiguus. To investigate the genomic basis of predation, we genome-sequenced 23 Corallococcus strains. Genomic similarity metrics grouped the sequenced strains into at least nine distinct genomospecies, divided between two major sub-divisions of the genus, encompassing previously described diversity. The Corallococcus pan-genome was found to be open, with strains exhibiting highly individual gene sets. On average, only 30.5% of each strain’s gene set belonged to the core pan-genome, while more than 75% of the accessory pan-genome genes were present in less than four of the 24 genomes. The Corallococcus accessory pan-proteome was enriched for the COG functional category “Secondary metabolism,” with each genome containing on average 55 biosynthetic gene clusters (BGCs), of which only 20 belonged to the core pan-genome. Predatory activity was assayed against ten prey microbes and found to be mostly incongruent with phylogeny or BGC complement. Thus, predation seems multifactorial, depending partially on BGC complement, but also on the accessory pan-genome – genes most likely acquired horizontally. These observations encourage further exploration of Corallococcus as a source for novel bioactive secondary metabolites and predatory proteins.

Predation is a fundamental ecological process, but within most microbial ecosystems the molecular mechanisms of predation remain poorly understood. We investigated transcriptome changes associated with the predation of Escherichia coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to pre-killed prey significantly altered expression of 1319 predator genes. However, the transcriptional response to living prey was minimal, with only 12 genes being significantly up-regulated. The genes most induced by prey presence (kdpA and kdpB, members of the kdp regulon) were confirmed by reverse transcriptase quantitative PCR to be regulated by osmotic shock in M. xanthus, suggesting indirect sensing of prey. However, the prey showed extensive transcriptome changes when co-cultured with predator, with 40 % of its genes (1534) showing significant changes in expression. Bacteriolytic M. xanthus culture supernatant and secreted outer membrane vesicles (OMVs) also induced changes in expression of large numbers of prey genes (598 and 461, respectively). Five metabolic pathways were significantly enriched in prey genes up-regulated on exposure to OMVs, supernatant and/or predatory cells, including those for ribosome and lipopolysaccharide production, suggesting that the prey cell wall and protein production are primary targets of the predator’s attack. Our data suggest a model of the myxobacterial predatome (genes and proteins associated with predation) in which the predator constitutively produces secretions which disable its prey whilst simultaneously generating a signal that prey is present. That signal then triggers a regulated feeding response in the predator.

Herpetosiphon spp. are ubiquitous, chemoheterotrophic, filamentous gliding bacteria with the ability to prey on other microbes through a “wolf pack” mechanism. The genus currently comprises four known species (H. aurantiacus, H. geysericola, H. giganteus, and H. gulosus), which produce antimicrobial secondary metabolites such as siphonazole. As part of a study isolating myxobacterial wolf pack predators, we serendipitously isolated a novel environmental strain (CA052B) from the edge of a stream at Llansteffan, United Kingdom, which was identified as a member of the Herpetosiphon genus. A lawn culture method was utilized to analyze the predatory activity of CA052B against 10 prey organisms of clinical relevance. CA052B was found to prey on Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Enterococcus faecalis, Bacillus subtilis, and Candida albicans. Purified CA052B outer membrane vesicles also exhibited killing activity against the prey organisms when tested by flow cytometry. 16S rRNA sequencing of CA052B showed 98 to 99% identity with other Herpetosiphon species members. Comparing the genome of CA052B with the publicly available genomes of H. aurantiacus and H. geysericola revealed average nucleotide identities of only 84% and 91%, respectively, whereas the genome-to-genome distance calculation showed sequence identities of 28.2% and 46.6%, respectively. Biochemical characterization also revealed distinctions between CA052B and both H. gulosus and H. giganteus. Thus, strain CA052B^T (= DSM 107618^T = NBRC 113495^T) is proposed to be the type strain of a novel species, Herpetosiphon llansteffanense sp. nov. The genome sequence of CA052B also revealed diverse secondary metabolite biosynthetic clusters, encouraging further exploration of its antibiotic production potential. IMPORTANCE Predatory bacteria are able to kill and consume other microbes and are therefore of interest as potential sources of new antimicrobial substances for applications in the clinic. “Wolf pack” predators kill prey by secreting antimicrobial substances into their surroundings, and those substances can kill prey organisms independently of the predatory cells. The genus Herpetosiphon exhibits wolf pack predation, yet its members are poorly described compared to other wolf pack predators, such as the myxobacteria. By providing a thorough characterization of a novel Herpetosiphon species, including its predatory, biochemical, and genomic features, this study increases our understanding of genomic variation within the Herpetosiphon genus and how that variation affects predatory activity. This will facilitate future rational exploitation of genus members (and other wolf pack predators) as sources of novel antimicrobials.

The coronavirus disease (COVID-19) is resulting in millions of infected individuals with several hundred thousands dead throughout the world. Amidst all the havoc, one interesting observation in the present COVID-19 pandemic is the negligible symptoms in the young; particularly children below 10 years of age. We assume the extensive pediatric vaccination with MMR vaccines followed globally could have resulted in innate immune responses, e.g., induction of interferons (IFNs) and activated natural killer (NK) cells, thereby offering natural immunity against SARS-CoV-2 in the young population. Possible cross-protective innate immunity offered by MMR vaccination prompted us to suggest repurposing MMR vaccination for immuno-prophylaxis against COVID-19.