Highly saturated P. gingivalis TnSeq libraries have been used to identify genes that are conditionally essential for (A) murine abscess formation [14]; (B) epithelial colonization [14]; (C) survival of cigarette smoke toxins [28]; (D) black pigmentation [12]; and (E) maintenance of a functional T9SS [27]. High throughput sequencing allows for the identification and quantification of multiple transposon insertion sites simultaneously among a large mixture of mutants. Varying library generation and analytical methods have been employed, while the technology is rapidly evolving, e.g., [21, 79–81]. Generally, however, subtraction of the sequenced output library (non-essential mutants) from the larger input library (essential and non-essential mutants) allows elucidation of those individual strains that are required for survival under a specific condition of interest and, so, unable to propagate, are absent or under-represented in the output library. Herein, we focus particularly on those P. gingivalis protease-encoding genes that are essential in several disease-related environments, assigning high potential therapeutic value to communal environmental fitness determinant(s).