“Tear down that wall” – updating the vocabulary of phage and bacterial lytic proteins

Lytic enzymes (often called lysins) break down the peptidoglycan, which in turn results in the death of bacteria. In consequence, they become one of the most promising alternatives to antibiotics. Such enzymes have been in the research spotlight and some of them have been proven to be effective and safe. The aim of this work was to gather the scattered data on functional and structural diversity of lysins, as well as available bioinformatic tools and data repositories used in studies of these proteins. 

In the introductory part of this paper, we disambiguate the terminology of lytic proteins, which, over the years, has grown to be inconsistent in different branches of science, and delineate major lysin groups. We also review the databases and programs, which can be harnessed in lysin studies, and put particular emphasis on repositories of Hidden Markov Models. Finally, we describe a comprehensive, meticulously curated set of lysin proteins, protein families and domains, and sort them into clusters that reflect major families. Thus this work is a guide through a convoluted tangle of terms, concepts, databases, models, approaches and programs used to detect lytic enzymes.

Methods
Original data were retrieved from:

http://biotechlab.fudan.edu.cn/database/EnzyBase

https://www.uniprot.org

Family/Domain databases:

http://eggnog5.embl.de (ver. 5.0)

http://pfam.xfam.org (ver. 33.0)

http://dmk-brain.ecn.uiowa.edu/pVOGs (accesed 01.02.2020)

https://vogdb.org (ver. vog99)

Proteins clustering (de-replication, MMseqs2 v 13.45111):

mmseqs easy-cluster ${rep_input_fasta} ${output_prefix} tmp --dbtype 1 --cov-mode 0 -c 0.8 --min-seq-id 0.9

HMMer quieries (hmmer v 3.1b2, http://hmmer.org/download.html):

hmmsearch --domtblout ${output_domtblout} --noali --cpu 15 ${derep_input_fasta} ${derep_input_fasta} &> ${log_file}"

HMM-HMM comparisons (hh-suite 3.3.0):

hhblits -i ${query_hmm} -d ${path_to_merged_databases_hhsuite} -o ${output_domtblout_hhr} -blasttab ${output_domtblout_btb}

Network visualisations were created using Cytoscape 3.9.1

Other analyses were conducted using scripts submitted to: https://github.com/zwmuam/lysin_vocabulary