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Page 2 of 19 Ambros et al. Microbiome Res Rep 2023;2:34 https://dx.doi.org/10.20517/mrr.2023.18

INTRODUCTION
Bacteriophages (short: phages, viruses specifically infecting bacterial cells) are known to negatively impact
food production and cause considerable losses in revenue when the fermenting microbiota are inhibited by
their antimicrobial activity, as seen in the dairy industry . Nonetheless, phages can also be advantageously
[1]
[2,3]
utilised, e.g., as additives to meat products to combat human pathogenic spoilage bacteria , or as
alternatives to antibiotics (phage therapy) in human health care .
[4]
Phages are divided into virulent and temperate phages, depending on their replication behaviour. After
infecting a bacterial host cell, virulent phages immediately hijack the translation and reproduction
mechanisms of their host and new phage progeny (virions) are released after host lysis, which is caused by
the interplay of different lysis proteins, such as holins and lysins (e.g., N-acetylmuramoyl-L-alanine
amidases) . In contrast, temperate phages can choose between the formerly described lytic life cycle, and
[5]
the lysogenic life cycle, where the phage genome is stably integrated into the bacterial chromosome. The
integrated phage genome is then called a prophage. In this life cycle, the prophage does not necessarily lyse
its host and is replicated during cell division along with the host chromosome. The conversion from
lysogenic into the lytic life cycle of temperate phages may occur spontaneously (spontaneous phage
[6]
induction; SPI) , but can also be forced by triggering the SOS response of the bacterial cell through DNA-
[7]
damaging phage inducers like UV light, and various antibiotics such as mitomycin C .
In contrast to the threat of lysogen depletion after their induction , prophages can also positively affect
[8]
their host’s fitness. Over the years, a multitude of different phage-derived mechanisms increasing host
fitness have been discovered, such as the transduction of beneficial genes like antibiotic resistance genes
(ARGs) to their host, or phage-encoded fitness factors like ADP-ribosyltransferases in Bacteroides that can
[9]
enhance the colonisation capabilities of their host . Furthermore, in Lactococcus lactis, the production of
[10]
membrane vesicles, mediated by phage-related lysis genes and used as “decoy” by the host, has been
[11]
discussed to reduce further phage infections . In summary, an analysis of prophage distribution and the
investigation of prophage-mediated functions can contribute to a deeper understanding of the competitive
advantages of certain strains.

A wide variety of studies have shown that (pro)phages are commonly found in lactic acid bacteria
(LAB) [7,12-14] . However, L. curvatus, a common starter organism in meat products serving as a bioprotective
agent against spoilage bacteria , has never been thoroughly screened for (pro)phages. L. curvatus is
[15]
regularly consumed in the human diet, mainly in association with fermented meat products . Moreover, it
[16]
was isolated from kimchi , sourdough , dairy products and honey , amongst others.
[20]
[19]
[17]
[18]
In a previous study, we examined the distribution and inducibility of prophages harboured within L. sakei
and demonstrated that temperate phages are tightly connected to this species . Considering that
[21]
L. curvatus and L. sakei are phylogenetically closely related and share similar ecological niches, L. curvatus is
a compelling potential host. Furthermore, recent publications evaluate the potential probiotic properties of
L. curvatus [17,22,23] . This discussion can benefit from phage-related data, as phages have the potential to carry
health-concerning genes such as toxins and are discussed to have a considerable impact on the
[24]
gastrointestinal health of humans .
[25]