Composer Kamala Sankaram’s last full-length chamber opera, “Thumbprint,” was set in Pakistan — the true story of a gang-rape victim who broke with tradition by taking her assailants to court instead of killing herself. Sankaram’s new work, however, is all-American.

“Taking Up Serpents,” the hour-long centerpiece of new works in this weekend’s American Opera Initiative of the Washington National Opera, is about Pentecostal snake-handlers in the South. These pastors use snakes and sometimes ingest poison, literally following a passage in the Gospel of Mark that says, “They shall take up serpents; and if they drink any deadly thing, it shall not hurt them; they shall lay hands on the sick, and they shall recover.” (In 2012, The Washington Post ran photos documenting the death of West Virginia pastor Randy “Mack” Wolford after a snakebite during a service.)

What makes an American opera? Companies across the country seem to be perpetually asking this question. The Metropolitan Opera is said to have turned down Rufus Wainwright’s opera “Prima Donna” on the grounds that it was in French and therefore not an American opera. Other companies turn to Hollywood — the Minnesota Opera has presented operatic versions of “The Shining” and “The Manchurian Candidate” — or book adaptations — the San Francisco Opera has offered “Dolores Claiborne” (based on the Stephen King novel) and “The Bonesetter’s Daughter” (based on the Amy Tan novel). Many of the support programs designed to promote new work create the somewhat amusing spectacle of American artists such as Sankaram, whose father is from South India, or the opera’s conductor, Lidiya Yankovskaya, whose family emigrated from Russia when she was 9, compressing themselves into someone else’s “American” template.

“Going into this opera, that worried me,” Yankovskaya says. “It’s much more difficult to express something you’re not intimately familiar with yourself. But then, of course, I’m not intimately familiar with what it’s like to be a courtesan in Europe,” which hasn’t stopped her from conducting “La traviata.”

“Taking Up Serpents” is loosely inspired by the nonfiction book “Salvation on Sand Mountain,” about a Pentecostal preacher who tried to use a snake to kill his wife, and by the experiences of the librettist, Jerre Dye, who grew up in the Pentecostal church. It delves deeply into a part of the American experience not usually documented on the opera stage. “The closest,” Sankaram says, “is ‘Susannah,’ ” Carlyle Floyd’s opera that retells the biblical parable of Susanna and the Elders, moving the action to the 20th-century American South.

But the new opera is mercifully free of assumed dialect or folksy musical Americana.

“It was important to us to try and put these people on the stage in a way that felt real,” says Sankaram, who aimed to create a sense of place with unusual orchestrations and particular instruments assigned to specific characters: a guitar for the Pentecostal preacher dying in the hospital of snakebite; a flute for the daughter, the central character, who travels home to see him.

“The opera opens in a mini-mart in the South,” Yankovskaya says. “The main character is standing outside under a fluorescent light; there is a moth. Kamala uses the flute to do these flutters, [showing] the moth in the light, [while the] piano and electric guitar hold out these chords. You feel like you’re under a fluorescent light in front of a minimart.”

Sankaram followed her own path into opera, from a small town in California where she fell in love with musical theater and began performing as a singer. (“Thumbprint” was a one-woman opera she wrote for herself.) Her father, however, disapproved of a musical career and offered to pay for graduate school as long as she didn’t study music. Hence Sankaram, along the way, picked up a doctorate in psychology. “I did a research degree studying how politics are framed by language and how reading news blogs changes the way people process information,” she says — today, a truly timely topic.

However, she says, “I couldn’t get any grant money to research on Twitter, but people started asking me to write more music.” Other works include “The Parksville Murders,” the first episode in what is described as “the world’s first virtual reality episodic horror opera.” (Sankaram is trying to get funding for the next episode.) She also has been working for several years on what she calls “an opera about data mining and algorithmic weaponization, loosely inspired by [Edward] Snowden,” in which audience members get a free drink if they sign a consent form that allows the creators to mine their public data; three audience members get personalized songs by the end of the evening.

Yankovskaya has been involved with “Taking Up Serpents” through the workshopping process, both in Washington and at a workshop the creative team set up with Mass Opera when they realized they weren’t going to get a chance in Washington to workshop the piece with the orchestra. (The score calls for 13 instruments, including long plastic tubes called whirly tubes that make noise when spun.) No stranger to creating work for the Chicago Opera Theater, which is workshopping Justine Chen’s “The Life and Death of Alan Turing” in conjunction with American Lyric Theater this season, Yankovskaya is enjoying coming in as a guest artist, able to focus on the music — and of being part of a creative team dominated by women. (The production’s stage director is Alison Moritz.)

Both Sankaram and Yankovskaya say they spent a lot of time thinking about the implications of Pentecostal worship. Sankaram says she tried to find musical expression of the intense symbolism with which Pentecostal followers imbue the world, incorporating elements such as numerology into her score. And Yankovskaya says she found parallels between speaking in tongues and the liberating power of music.

“It seems to me that speaking in tongues is a beautiful way for people to find freedom and release from the constraints of their culture and society,” she says. “It’s a true kind of release, finding something totally outside oneself that most of us don’t experience in our lives. . . . When we’re in touch with the music we’re creating, and just are one with the music, that’s like this type of worship.”

The Washington National Opera’s “Taking Up Serpents” Friday at 7:30 p.m. and Jan. 13 at 2 p.m. in the Kennedy Center’s Terrace Theater.