ABSTRACTPathogenic microbial ecosystems are often polymicrobial, and interbacterial interactions drive emergent properties of these communities. In the oral cavity,Streptococcus gordoniiis a foundational species in the development of plaque biofilms, which can contribute to periodontal disease and, after gaining access to the bloodstream, target remote sites such as heart valves. Here, we used a transposon sequencing (Tn-Seq) library ofS. gordoniito identify genes that influence fitness in a murine abscess model, both as a monoinfection and as a coinfection with an oral partner species,Porphyromonas gingivalis. In the context of a monoinfection, conditionally essential genes were widely distributed among functional pathways. Coinfection withP. gingivalisalmost completely changed the nature ofin vivogene essentiality. Community-dependent essential (CoDE) genes under the coinfection condition were primarily related to DNA replication, transcription, and translation, indicating that robust growth and replication are required to survive withP. gingivalisin vivo. Interestingly, a group of genes in an operon encoding streptococcal receptor polysaccharide (RPS) were associated with decreased fitness ofS. gordoniiin a coinfection withP. gingivalis. Individual deletion of two of these genes (SGO_2020 and SGO_2024) resulted in the loss of RPS production byS. gordoniiand increased susceptibility to killing by neutrophils.P. gingivalisprotected the RPS mutants by inhibiting neutrophil recruitment, degranulation, and neutrophil extracellular trap (NET) formation. These results provide insight into genes and functions that are important forS. gordoniisurvivalin vivoand the nature of polymicrobial synergy withP. gingivalis. Furthermore, we show that RPS-mediated immune protection inS. gordoniiis dispensable and detrimental in the presence of a synergistic partner species that can interfere with neutrophil killing mechanisms.